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PubMed1983

An assessment of the evidence for the role of ribonucleoprotein particles in the maturation of eukaryote mRNA.

This article has sought to draw together, on the one hand, what is known of mRNA processing and its control and, on the other hand, what is known of the structure and validity of hnRNP and snRNP particles. At the same time, it has attempted to synthesize these two themes into a critical assessment of the evidence which suggests that the particles are intimately involved in processing. It cannot be said that the case is proven. The evidence is compelling but circumstantial. The last few years have seen the development of the first in vitro splicing systems (Weingartner and Keller, 1981; Goldenberg and Raskus, 1981; Kole and Weissman, 1982), the isolation of monoclonal antibodies to defined snRNP (Lerner et al., 1981a; Billings et al., 1982) and hnRNP proteins (Hugle et al., 1982), and the ability to use artificial lipid vesicles to transfer antisera (Lenk et al., 1982) and radioactive snRNA (Gross and Cetron, 1982) into cells. It is to be hoped that further refinements of these and other techniques will allow us to solve this, one of the major outstanding problems of molecular biology.

Animals↗
PubMed1985

Accurate cleavage and polyadenylation of exogenous RNA substrate.

Purified precursor RNA containing the L3 polyadenylation site of late adenovirus 2 mRNA is accurately cleaved and polyadenylated when incubated with nuclear extract from HeLa cells. The reaction is very efficient; 75% of the precursor is correctly processed. Cleavage is rapidly followed by polymerization of an initial poly(A) tract of approximately 130 nucleotides. Additional adenosine residues are added during further incubation. In the presence of the ATP analog alpha-beta-methylene-adenosine 5' triphosphate, the precursor RNA is cleaved but not polyadenylated, suggesting that processing is not coupled to the synthesis of the initial poly(A) tract. In the absence of free Mg2+, a small RNA of approximately 46 nucleotides is stabilized against degradation. Fingerprint analysis suggests this RNA is produced by endonucleolytic cleavage at the L3 site. Like the in vitro splicing reaction, the in vitro polyadenylation reaction is inhibited by adding antiserum against the small nuclear ribonucleoprotein particle containing U1 RNA.

Adenosine Triphosphate↗
PubMed1996

The SLA RNA gene of Trypanosoma brucei is organized in a tandem array which encodes several small RNAs.

We have recently identified the Spliced Leader Associated RNA (SLA RNA) which is implicated in pre-messenger RNA splicing in Trypanosoma brucei by virtue of its interaction with the 5' splice site of the trans spliced spliced leader RNA (SL RNA) in vivo. Southern analyses reveal that the SLA RNA gene is found in a tandem array of 10-11 copies per haploid genome in T. brucei. Each repeat unit in the array encodes three additional small RNAs of unknown function. RNA polymerase inhibition studies are consistent with transcription of all four genes by the same polymerase, but do not clearly differentiate between RNA polymerases II and III. The SLA RNA has homologs in other kinetoplastid protozoa and we have determined the sequence from two additional species. Trypanosoma cruzi and Crithidia fasciculata. Features of both secondary structure and sequence are conserved in these organisms. One conserved element, 5'-UGUAGUG-3', has the potential to base-pair to the SL RNA upstream of the 5' splice site. This potential interaction is consistent with the sites of SL RNA to SLA RNA psoralen cross-linking in vivo [1].

Animals↗
PubMed1992

Regulation of macromolecular traffic mediated by the nuclear pore complex.

A sophisticated selective mechanism that regulates nuclear-cytoplasmic traffic has evolved in eukaryotes which circumvents the formidable barrier presented by the nuclear envelope. The sites of RNA and protein exchanges are the nuclear pore complexes (NPCs), 125 MDa supramolecular assemblies inserted into the envelope (see recent reviews by Dingwall, 1991; Goldfarb and Michaud, 1991; Miller et al., 1991; Nigg et al., 1991). In this article, the role NPCs play in regulating intracellular macromolecular traffic will be discussed.

Animals↗
PubMed2000

Functions of Lsm proteins in mRNA degradation and splicing.

Recent results have identified a family of Lsm (Like Sm) proteins that are related to the Sm protein family. Seven Lsm proteins form a complex, which interacts with the U6 snRNA and functions in splicing. In addition, a different complex of Lsm proteins interacts with cytoplasmic mRNA and promotes its turnover. These diverse functions of Lsm proteins suggest that they are important modulators of RNA biogenesis and function.

Humans↗
PubMed2002

Messenger RNA degradation: beginning at the end.

The mechanisms responsible for mRNA decay in mammalian cells, and how specific sequence elements accelerate decay, are unknown. Recent work indicates that 'ARE' instability elements recruit the exosome to promote rapid 3'-to-5' degradation of the mRNA.

3' Untranslated Regions↗
PubMed2003

Translation initiation and viral tricks.

A variety of viral strategies are utilized for dominance of the host-cell protein synthetic machinery, optimization of viral mRNA translation and evasion of host-cell antiviral responses that act at the translational level. Many viruses exploit regulated steps in the initiation of cellular protein synthesis to their own advantage. They have developed some rather unconventional means for mRNA translation, which were probably adapted from specialized cellular mRNA translation systems. Regardless of the type of translational tricks exploited, viruses typically ensure efficient viral translation, often at the expense of host-cell protein synthesis.

Animals↗
PubMed2002

Path of an RNA ligand around the surface of the vaccinia VP39 subunit of its cognate VP39-VP55 protein heterodimer.

VP39 is a vaccinia virus-encoded RNA modifying protein with roles in the modification of both mRNA ends. At the 3' end it acts as a processivity factor for the vaccinia poly(A) polymerase (VP55), promoting poly(A) tail elongation. Despite VP39's three-dimensional structure having been elucidated along with details of its mode of mRNA 5' end binding, the VP39-VP55 heterodimer's molecular mechanism of processivity is largely unknown. Here, the area immediately above almost the entire surface of the VP39 subunit was probed using chemical reporters, and the path of a previously unidentified RNA binding site was revealed. The path was indicated to fall within a cleft formed by the intersubunit interface and was consistent with both a previously reported model of the heterodimer-nucleic acid ternary complex and the known function of the heterodimer in processive poly(A) tail elongation.

Binding Sites↗
PubMed2004

Emerging genomic and proteomic evidence on relationships among the animal, plant and fungal kingdoms.

Sequence-based molecular phylogenies have provided new models of early eukaryotic evolution. This includes the widely accepted hypothesis that animals are related most closely to fungi, and that the two should be grouped together as the Opisthokonta. Although most published phylogenies have supported an opisthokont relationship, a number of genes contain a tree-building signal that clusters animal and green plant sequences, to the exclusion of fungi. The alternative tree-building signal is especially intriguing in light of emerging data from genomic and proteomic studies that indicate striking and potentially synapomorphic similarities between plants and animals. This paper reviews these new lines of evidence, which have yet to be incorporated into models of broad scale eukaryotic evolution.

Animals↗