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PubMed1999

Long RNA hairpins that contain inosine are present in Caenorhabditis elegans poly(A)+ RNA.

Adenosine deaminases that act on RNA (ADARs) are RNA-editing enzymes that convert adenosine to inosine within double-stranded RNA. In the 12 years since the discovery of ADARs only a few natural substrates have been identified. These substrates were found by chance, when genomically encoded adenosines were identified as guanosines in cDNAs. To advance our understanding of the biological roles of ADARs, we developed a method for systematically identifying ADAR substrates. In our first application of the method, we identified five additional substrates in Caenorhabditis elegans. Four of those substrates are mRNAs edited in untranslated regions, and one is a noncoding RNA edited throughout its length. The edited regions are predicted to form long hairpin structures, and one of the RNAs encodes POP-1, a protein involved in cell fate decisions.

3' Untranslated Regions↗

PubMed1996

G alpha i RNA antisense expression demonstrates the exclusive coupling of peptide YY receptors to G(i)2 proteins in renal proximal tubule cells.

A clone PKSV-PCT Cl.10 referred to as Cl.10 was selected from the PKSV-PCT renal proximal tubule cell line which expressed peptide YY (PYY) receptors (Voisin, T., Bens, M., Cluzeaud, F., Vandewalle, A., and Laburthe, M. (1993) J. Biol. Chem. 268, 20547-20554). In order to identify G(i) protein(s) coupled to PYY receptors, antisense G alpha i protein RNAs were expressed in Cl.10 cells by transfecting the pcDNA3 vector into which were inserted 39 bases of the 5'-noncoding region of G alpha i2 or G alpha i3 used as specific antisense templates. A Cl.10/alpha i2-clone was selected which displayed a drastic decrease (> 90%) of the expression of G alpha i2 without changes of G alpha i3, G alpha s, and G beta subunits (G alpha i1 is not present in Cl.10 cells) as evidenced by Western blots. When compared to untransfected cells, this clone exhibited: (i) an increase in the dissociation constant of PYY receptors (5.3 versus 0.6 nM) identical to that observed in pertussis toxin-treated untransfected cells; (ii) an absence of inhibition of 125I-PYY binding by guanosine 5'-O-(thiotriphosphate) (GTP gamma S); and (iii) the failure of PYY to inhibit cAMP levels and to stimulate [methyl-3H]thymidine incorporation into DNA. A clone was also selected which exhibited a specific decrease (> 80%) of G alpha i3 as compared to untransfected cells. The sensitivity to GTP gamma S and the dissociation constant of PYY receptors as well as PYY-mediated inhibition of cAMP were identical to those observed in untransfected cells. These findings support an exclusive coupling of PYY receptors to G alpha i2.

Animals↗

PubMed1980

Topography of the three late mRNA's of polyoma virus which encode the virion proteins.

The three cytoplasmic polyadenylated mRNA's which separately encode the three capsid proteins (VP1, VP2, and VP3) of polyoma virus were mapped on the viral genome by one- and two-dimensional gel electrophoreses of nuclease S1-resistant RNA-DNA hybrids. The mRNA's, which we designated mVP1, mVP2, and mVP3 to indicate the coding functions deduced from the cosedimentation of the RNAs and the messenger activities, comprise an overlapping set of 3'-coterminal molecules which also share a heterogeneous family of noncoding 5'-terminal regions (Flavell et al., Cell 16:357--371, 1979; Legon et al., Cell 16:373--388, 1979). The three species differ in the length of the 3' colinear coding region which is spliced to the 5' leader sequences. The common polyadenylated 3' end maps at map unit 25.3. The 5' ends of the colinear bodies of mVP1, mVP3, and mVP2 map at 48.5, 59.5, and 66.5 map units, respectively. An examination of the polyoma virus DNA sequence (Arrand et al., J. Virol. 33:606--618, 1980) in the vicinities of splicing sites approximated by the S1 gel mapping data for sequences common to the ends of known intervening sequences allowed prediction of the precise splice points in polyoma virus late mRNA's. In all three cases, the leader sequences are joined to the mRNA bodies at least 48 nucleotides before the translational initiation codon used in each particular messenger. The start signal which functions in each mRNA is the first AUG (or GUG) triplet after the splice junction.

Capsid↗

PubMed1991

Oral poliovirus vaccine in the United States: molecular characterization of Sabin type 3 after replication in the gut of vaccinees.

Derivatives of Sabin 3 shed from recipients of oral poliovirus vaccine in the United States (U.S.) were examined for genetic changes identified in strains excreted by vaccinees in the United Kingdom [U.K.; Evans et al., 1985; Cammack et al., 1988, Macadam et al., 1989]. Among the eight primary vaccinees studied, the duration of excretion and molecular evolution of type 3 strains varied greatly. The period of virus excretion after vaccination ranged from as few as 2 days to as many as 36 days. Nucleotide sequence analysis of viral RNAs extracted from shed virus indicated that only fifty percent of the vaccinees exclusively excreted strains in which the attenuating mutation at nucleotide 472 in the 5' noncoding region of the genome had reverted from uracil (U) to cytosine (C), the nucleotide found in neurovirulent strains. Compared to the wild-type Leon strain, the low activity of stool isolate KW4 in a complete monkey neurovirulence test demonstrated that presence of C at 472 does not render a type 3 strain pathogenic. Conversely, an isolate was identified which efficiently replicated in monkey nervous tissue and maintained the attenuated U at 472. Oligonucleotide fingerprinting and sequence analysis of viral RNAs from stool isolates indicated that one vaccinee (KW) eventually excreted intertypic recombinant strains consistent with those reported in the U.K. studies. Unique to this study, one vaccinee (KS) excreted nonrecombinant virus possessing U at 472 for up to 21 days. The significance of the KS strain profile in relation to differences in the U.S. vaccine compared to the vaccine distributed in the U.K. and other countries is discussed.

Animals↗

PubMed1994

Low frequency of detection by nested polymerase chain reaction of enterovirus ribonucleic acid in endomyocardial tissue of patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine the prevalence of enteroviral infection in the myocardium of patients with idiopathic dilated cardiomyopathy by using a highly sensitive and specific detection technique. BACKGROUND: Recent molecular studies have suggested that enteroviral persistence (in particular, coxsackieviruses type B) may underlie idiopathic myocarditis and dilated cardiomyopathy. METHODS: The method used to detect enterovirus-specific ribonucleic acids (RNAs) is based on reverse transcription and nested polymerase chain reaction amplification with four pairs of primers from the conserved 5' noncoding region of the enteroviral genome. Several members of the Enterovirus genus are detectable by this assay (coxsackieviruses B1 to B6; polioviruses 1 to 3; echoviruses 9, 19 and 31), with a sensitivity threshold close to the detection of a single molecule of viral RNA in 1 mg of tissue sample. Endomyocardial tissue samples from 84 subjects were analyzed (77 samples obtained from left endomyocardial biopsies, 7 from explanted hearts). The subjects comprised 63 study patients (53 with dilated cardiomyopathy, 3 with idiopathic myocarditis, 1 with right ventricular dysplasia, 1 with restrictive cardiomyopathy, 1 with eosinophilic myocarditis, 1 with primary ventricular fibrillation and 3 with myocarditis of known etiology) and 21 control subjects with other diseases. RESULTS: Positive signals were obtained only in samples from six study patients (four with dilated cardiomyopathy, one with right ventricular dysplasia and one with myocarditis). Samples from control subjects, uninfected rat myocardium and cultured cell lines yielded systematically negative results. Moreover, the nucleotide sequence analysis of the amplification products from patients with positive samples raised doubts about the true positivity of these samples. CONCLUSIONS: This study suggests that the persistence of enteroviral RNA in dilated cardiomyopathy is not a major cause of the disease and that a careful analysis of polymerase chain reaction amplification products is essential in any study in which this technique is pushed to high sensitivity thresholds.

Adult↗

PubMed1993

Use of genomic probes to detect hepatitis A virus and enterovirus RNAs in wild shellfish and relationship of viral contamination to bacterial contamination.

Genomic probes were used to investigate hepatitis A virus (HAV) and enterovirus RNAs in two types of shellfish from natural beds (Atlantic coast, France). After elution concentration, nucleic acid extracted by proteinase K and purified by phenol-chloroform and ethanol precipitation was assayed by dot blot hybridization. The probes used were a specific HAV probe corresponding to the 3' end (3D polymerase coding region) and an enterovirus probe corresponding to the 5' noncoding region. The method was first tested under experimental conditions by using virus-spiked shellfish before being applied under field conditions. Our results show that shellfish were highly contaminated: enterovirus and HAV RNAs were found in 63 and 67%, respectively, of samples examined with the riboprobes. On the same site, viral (HAV and enterovirus) RNAs were found in a larger fraction of cockles than mussels. Statistical tests of dependence showed no relationship between viral contamination and bacterial contamination (evaluated by fecal coliform counts).

Animals↗

PubMed1999

Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements.

The translation of picornavirus genomic RNAs occurs by a cap-independent mechanism that requires the formation of specific ribonucleoprotein complexes involving host cell factors and highly structured regions of picornavirus 5' noncoding regions known as internal ribosome entry sites (IRES). Although a number of cellular proteins have been shown to be involved in picornavirus RNA translation, the precise role of these factors in picornavirus internal ribosome entry is not understood. In this report, we provide evidence for the existence of distinct mechanisms for the internal initiation of translation between type I and type II picornavirus IRES elements. In vitro translation reactions were conducted in HeLa cell cytoplasmic translation extracts that were depleted of the cellular protein, poly(rC) binding protein 2 (PCBP2). Upon depletion of PCBP2, these extracts possessed a significantly diminished capacity to translate reporter RNAs containing the type I IRES elements of poliovirus, coxsackievirus, or human rhinovirus linked to luciferase; however, the addition of recombinant PCBP2 could reconstitute translation. Furthermore, RNA electrophoretic mobility-shift analysis demonstrated specific interactions between PCBP2 and both type I and type II picornavirus IRES elements; however, the translation of reporter RNAs containing the type II IRES elements of encephalomyocarditis virus and foot-and-mouth disease virus was not PCBP2 dependent. These data demonstrate that PCBP2 is essential for the internal initiation of translation on picornavirus type I IRES elements but is dispensable for translation directed by the structurally distinct type II elements.

5' Untranslated Regions↗

PubMed1998

Recombinant dengue virus type 1 NS3 protein exhibits specific viral RNA binding and NTPase activity regulated by the NS5 protein.

The full-length dengue virus NS3 protein has been successfully expressed as a 94-kDa GST fusion protein in Escherichia coli. Treatment of the purified fusion protein with thrombin released a 68-kDa protein which is the expected molecular mass for the DEN1 NS3 protein. The identity of this protein was confirmed by Western blotting using dengue virus antisera. Two related activities of the recombinant NS3 protein were characterized, which were the binding of the protein to the 3'-noncoding region of the dengue virus RNA genome and NTPase activity. We demonstrated using a band shift assay that the DEN1 NS3 protein could form a complex with the stem-loop structure in the 3'-noncoding region (3'-NCR), although sites outside the stem-loop may also participate in binding. Using various unlabeled homopolymeric and heteropolymeric RNAs as competitors for binding, it was further shown that the DEN1 NS3 protein exhibits preferential binding to a 94-nt RNA transcript from the 3'-NCR of the dengue virus. The NTPase activity of the recombinant DEN1 NS3 protein was characterized using a thin-layer chromatography assay. We found that the DEN1 NS3 protein possesses some aspects of NTPase activity, which are distinct from those found in other flaviviruses. Although the NS3 protein was able to utilize all four ribonucleoside triphosphates as its substrates, the NS3 protein showed a distinct preference for purine triphosphates (i.e., ATP and GTP). The addition of poly(U) did not stimulate NTPase activity in DEN1 NS3 protein, which contrasts with the reports for other flaviviral NS3 proteins. However, NTPase activity was specifically stimulated by the viral NS5 protein, which was manifested by a more than twofold increase in the rate of ATP hydrolysis and a 25% increase in the yield of ADP at the end of a 120-min reaction. These data suggest that the NTPase activity of the NS3 protein may be regulated by the viral NS5 protein during virus replication.

Adenosine Triphosphatases↗

PubMed1992

Reversion of Q beta RNA phage mutants by homologous RNA recombination.

Q beta phage RNAs with inactivating insertion (8-base) or deletion (17-base) mutations within their replicase genes were prepared from modified Q beta cDNAs and transfected into Escherichia coli spheroplasts containing Q beta replicase provided in trans by a resident plasmid. Replicase-defective (Rep-) Q beta phage produced by these spheroplasts were detected as normal-sized plaques on lawns of cells containing plasmid-derived Q beta replicase, but were unable to form plaques on cells lacking this plasmid. When individual Rep- phage were isolated and grown to high titer in cells containing plasmid-derived Q beta replicase, revertant (Rep+) Q beta phage were obtained at a frequency of ca. 10(-8). To investigate the mechanism of this reversion, a point mutation was placed into the plasmid-derived Q beta replicase gene by site-directed mutagenesis. Q beta mutants amplified on cells containing the resultant plasmid also yielded Rep+ revertants. Genomic RNA was isolated from several of the latter phage revertants and sequenced. Results showed that the original mutation (insertion or deletion) was no longer present in the phage revertants but that the marker mutation placed into the plasmid was now present in the genomic RNAs, indicating that recombination was one mechanism involved in the reversion of the Q beta mutants. Further experiments demonstrated that the 3' noncoding region of the plasmid-derived replicase gene was necessary for the reversion-recombination of the deletion mutant, whereas this region was not required for reversion or recombination of the insertion mutant. Results are discussed in terms of a template-switching model of RNA recombination involving Q beta replicase, the mutant phage genome, and plasmid-derived replicase mRNA.

Amino Acid Sequence↗

PubMed2002

RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA.

Adenosine deaminases that act on RNA (ADARs) constitute a family of RNA-editing enzymes that convert adenosine to inosine within double-stranded regions of RNA. We previously developed a method to identify inosine-containing RNAs and used it to identify five ADAR substrates in Caenorhabditis elegans. Here we use the same method to identify five additional C. elegans substrates, including three mRNAs that encode proteins known to affect neuronal functions. All 10 of the C. elegans substrates are edited in long stem-loop structures located in noncoding regions, and thus contrast with previously identified substrates of other organisms, in which ADARs target codons. To determine whether editing in noncoding regions was a conserved ADAR function, we applied our method to poly(A)+ RNA of human brain and identified 19 previously unknown ADAR substrates. The substrates were strikingly similar to those observed in C. elegans, since editing was confined to 3' untranslated regions, introns, and a noncoding RNA. Also similar to what was found in C. elegans, 15 of the 19 substrates were edited in repetitive elements. The identities of the newly identified ADAR substrates suggest that RNA editing may influence many biologically important processes, and that for many metazoa, A-to-I conversion in coding regions may be the exception rather than the rule.

3' Untranslated Regions↗

PubMed1998

The rhinovirus type 14 genome contains an internally located RNA structure that is required for viral replication.

Cis-acting RNA signals are required for replication of positive-strand viruses such as the picornaviruses. Although these generally have been mapped to the 5' and/or 3' termini of the viral genome, RNAs derived from human rhinovirus type 14 are unable to replicate unless they contain an internal cis-acting replication element (cre) located within the genome segment encoding the capsid proteins. Here, we show that the essential cre sequence is 83-96 nt in length and located between nt 2318-2413 of the genome. Using dicistronic RNAs in which translation of the P1 and P2-P3 segments of the polyprotein were functionally dissociated, we further demonstrate that translation of the cre sequence is not required for RNA replication. Thus, although it is located within a protein-coding segment of the genome, the cre functions as an RNA entity. Computer folds suggested that cre sequences could form a stable structure in either positive- or minus-strand RNA. However, an analysis of mutant RNAs containing multiple covariant and non-covariant nucleotide substitutions within these putative structures demonstrated that only the predicted positive-strand structure is essential for efficient RNA replication. The absence of detectable minus-strand synthesis from RNAs that lack the cre suggests that the cre is required for initiation of minus-strand RNA synthesis. Since a lethal 3' noncoding region mutation could be partially rescued by a compensating mutation within the cre, the cre appears to participate in a long-range RNA-RNA interaction required for this process. These data provide novel insight into the mechanisms of replication of a positive-strand RNA virus, as they define the involvement of an internally located RNA structure in the recognition of viral RNA by the viral replicase complex. Since internally located RNA replication signals have been shown to exist in several other positive-strand RNA virus families, these observations are potentially relevant to a wide array of related viruses.

Amino Acid Sequence↗

PubMed1995

Sequence and structural determinants of the interaction between the 5'-noncoding region of picornavirus RNA and rhinovirus protease 3C.

It has previously been established that human rhinovirus 14 protease 3C binds specifically to the 5'-noncoding region of the viral RNA. A series of mutants of protease 3C and deletion or point mutants of the 5'-noncoding region of the viral RNA were analyzed to elucidate the sites of interaction between the protease and the RNA. Amino acids in protease 3C essential for RNA binding were found to be discontinuous in the amino acid sequence, and mutations which destroyed RNA binding did not affect the catalytic (proteolytic) activity of protease 3C. Based on the three-dimensional structure of rhinovirus 14 protease 3C, the RNA binding region is located in an extended area distinct from the catalytic triad. A single stem-loop structure of 27 nucleotides (stem-loop d) in the 5'-noncoding region was necessary and sufficient to bind protease 3C. Mutagenesis of either the base-paired stem or unpaired loop or bulge regions of stem-loop d suggested that the base-paired stem, but not the loop or bulge, carries important determinants of protease 3C binding. This conclusion is strengthened by the observation that rhinovirus 14 protease 3C bound specifically to the 5'-noncoding region of poliovirus RNA, and only the base-paired stem of stem-loop d is conserved between poliovirus and rhinovirus RNAs.

3C Viral Proteases↗

PubMed1993

Biochemical and genetic evidence for a pseudoknot structure at the 3' terminus of the poliovirus RNA genome and its role in viral RNA amplification.

The sequences in the plus-stranded poliovirus RNA genome that dictate the specific amplification of viral RNA in infected cells remain unknown. We have analyzed the structure of the 3' noncoding region of the viral genome by thermodynamic-based structure calculation and by chemical and enzymatic probing of in vitro-synthesized RNAs and provide evidence for the existence of an RNA pseudoknot structure in this region. To explore the functional significance of this structure, revertants of a mutant bearing a lesion in the proposed pseudoknot and exhibiting a temperature-sensitive defect in viral RNA synthesis were isolated and mapped. The results of this genetic analysis established a correlation between the structure of the 3' terminus of the viral RNA and its function in vivo in RNA amplification. Furthermore, phylogenetic analysis indicated that a similar structure could be formed in coxsackievirus B1, a related enterovirus, which further supports a role for the pseudoknot structure in viral RNA amplification in infected cells.

Base Sequence↗

PubMed2024

Transcriptome-wide N6-methyladenosine modification profiling of long non-coding RNAs in patients with recurrent implantation failure.

N6-methyladenosine (m6A) is involved in most biological processes and actively participates in the regulation of reproduction. According to recent research, long non-coding RNAs (lncRNAs) and their m6A modifications are involved in reproductive diseases. In the present study, using m6A-modified RNA immunoprecipitation sequencing (m6A-seq), we established the m6A methylation transcription profiles in patients with recurrent implantation failure (RIF) for the first time. There were 1443 significantly upregulated m6A peaks and 425 significantly downregulated m6A peaks in RIF. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that genes associated with differentially methylated lncRNAs are involved in the p53 signalling pathway and amino acid metabolism. The competing endogenous RNA network revealed a regulatory relationship between lncRNAs, microRNAs and messenger RNAs. We verified the m6A methylation abundances of lncRNAs by using m6A-RNA immunoprecipitation (MeRIP)-real-time polymerase chain reaction. This study lays a foundation for further exploration of the potential role of m6A modification in the pathogenesis of RIF.

Humans↗

PubMed1999

Enhancer-like properties of an RNA element that modulates Tombusvirus RNA accumulation.

Prototypical defective interfering (DI) RNAs of the plus-strand RNA virus tomato bushy stunt virus contain four noncontiguous segments (regions I-IV) derived from the viral genome. Region I corresponds to 5'-noncoding sequence, regions II and III are derived from internal positions, and region IV represents a 3'-terminal segment. We analyzed the internally located region III in a prototypical DI RNA to understand better its role in DI RNA accumulation. Our results indicate that (1) region III is not essential for DI RNA accumulation, but molecules that lack it accumulate at significantly reduced levels ( approximately 10-fold lower), (2) region III is able to function at different positions and in opposite orientations, (3) a single copy of region III is favored over multiple copies, (4) the stimulatory effect observed on DI RNA accumulation is not due to region III-mediated RNA stabilization, (5) DI RNAs lacking region III permit the efficient accumulation of head-to-tail dimers and are less effective at suppressing helper RNA accumulation, and (6) negative-strand accumulation is also significantly depressed for DI RNAs lacking region III. Collectively, these results support a role for region III as an enhancer-like element that facilitates DI RNA replication. A scanning-type mutagenesis strategy was used to define portions of region III important for its stimulatory effect on DI RNA accumulation. Interestingly, the results revealed several differences in the requirements for activity when region III was in the forward versus the reverse orientation. In the context of the viral genome, region III was found to be essential for biological activity. This latter finding defines a critical role for this element in the reproductive cycle of the virus.

Base Sequence↗

PubMed2002

Trans-splicing in Drosophila.

Splicing is an efficient and precise mechanism that removes noncoding regions from a single primary RNA transcript. Cutting and rejoining of the segments occurs on nascent RNA. Trans-splicing between small specialized RNAs and a primary transcript has been known in some organisms but recent papers show that trans-splicing between two RNA molecules containing different coding regions is the normal mode in a Drosophila gene. The mod(mdg4) gene produces 26 different mRNAs encoding as many protein isoforms. The differences lie in alternative 3' exons encoded by different transcriptional units and spliced to the 5' common region by a surprising trans-splicing mechanism.

Animals↗

PubMed1983

Homologous nucleotide sequences at the 5' termini of messenger RNAs synthesized from the yeast enolase and glyceraldehyde-3-phosphate dehydrogenase gene families. The primary structure of a third yeast glyceraldehyde-3-phosphate dehydrogenase gene.

Genomic DNA containing a third yeast glyceraldehyde-3-phosphate dehydrogenase structural gene has been isolated on a bacterial plasmid designated pgap11. The complete nucleotide sequence of this structural gene was determined. The gene contains no intervening sequences, codon usage is highly biased, and the nucleotide sequence of the coding portion of this gene is 90% homologous to the other two glyceraldehyde-3-phosphate dehydrogenase genes (Holland, J. P., and Holland, M. J. (1980) J. Biol. Chem. 255, 2596-2605). Based on the extent of nucleotide sequence divergence among the three glyceraldehyde-3-phosphate dehydrogenase genes, it is likely that they arose as a consequence of two duplication events and the gene contained on the hybrid plasmid designated pgap11 is a product of the first duplication event. All three structural genes share extensive nucleotide sequence homology in the 5'-noncoding regions adjacent to the three respective translational initiation codons. The gene contained on pgap11 is not homologous to the others downstream from the respective translational termination codon, however. The 5' termini of messenger RNAs synthesized from the three glyceraldehyde-3-phosphate dehydrogenase and two yeast enolase genes have been mapped to sites ranging from 36 to 82 nucleotides upstream from the respective translational initiation codons. In each case the 5' terminus of the mRNA maps to a region of strong nucleotide sequence homology which is shared by all five structural genes. These latter data confirm that all five structural genes are expressed during vegetative cell growth and further support the hypothesis that a portion of the 5'-noncoding flanking region of the yeast glyceraldehyde-3-phosphate dehydrogenase and enolase genes evolved from a common precursor sequence.

Base Sequence↗

PubMed1999

SR protein kinases: the splice of life.

The eukaryotic genome codes for most of its proteins though discontinuous coding sequences called exons, which are separated by noncoding sequences known as introns. Following transcription of a gene, these exons must be spliced precisely, removing the intervening introns, to form meaningful mature messenger RNAs (mRNA) that are transported to the cytoplasm and translated by the ribosomal machinery. To add yet another level of complexity, a process known as alternative splicing exists, whereby a single pre-mRNA can give rise to two or more mature mRNAs depending on the combination of exons spliced together. Alternative splicing of pre-mRNAs is emerging as an important mechanism for gene regulation in many organisms. The classic example of splicing as a regulator of genetic information during a developmental process is sex determination in Drosophila. The now well-characterized cascade of sex-specific alternative splicing events demonstrates nicely how the control of splice site selection during pre-mRNA processing can have a profound effect on the development of an organism. The factors involved in pre-mRNA splicing and alternative splice site selection have been the subject of active study in recent years. Emerging from these studies is a picture of regulation based on protein-protein, protein-RNA, and RNA-RNA interactions. How the interaction of the various splicing constituents is controlled, however, is still poorly understood. One of the mechanisms of regulation that has received attention recently is that of posttranslational phosphorylation. In the following article, we cite the evidence for a role of phosphorylation in constitutive and alternative splicing and discuss some of the recent information on the biochemistry and biology of the enzymes involved.

Alternative Splicing↗