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PubMedDate not supplied

Cytotoxic ribonucleases and RNA interference (RNAi).

Several cytotoxic ribonucleases (CRs), homologs of the pancreatic RNase A, have been isolated from amphibian oocytes or embryos. Of them, onconase (Onc), the CR that shows antitumor properties and is in phase III clinical trials, was the most extensively researched. Degradation of tRNA by Onc internalized into cells that leads to inhibition of protein synthesis is considered the mechanism of its cytotoxicity. Several findings, however, cannot be explained by nonspecific decline in protein synthesis alone and suggest additional or alternative mechanism(s). We postulate therefore that miRNAs and/or RNA interference (RNAi) may also be targets of CRs. The following arguments support this postulate: (A) miRNAs and siRNAs appear to be unprotected by proteins and therefore, as tRNA, accessible and degradable by CRs; (B) Onc has preferred cleavage sites on tRNAs: their cleavage may generate segments of dsRNA that interfere with translation. Analogous to Dicer, thus, small RNAs with interfering properties may be generated by CRs within the cell; (C) CRs are abundant in oocytes and during embryonic development; their role there is unknown. Since cells undergo perpetual differentiation during embryogenesis it is likely that the function of CRs is to provide additional level of regulation of gene expression via the mechanisms listed in (A) and/or (B).

Animals↗
PubMed2004

[Advances in the molecular mechanism of RNA interference].

This paper reviews the latest development of RNA interference(RNAi). RNA interference is the process of sequence-specific degradation of homologous mRNA triggered by double-stranded RNA. As a technically simple and an effective genetic tool which can exert effect on the expression of gene and substitute for gene knock-out technique in some degree, RNAi phenomena have been broadly validated in diverse model organisms such as Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana and Neurospora crassa. Simultaneously, study on molecular mechanism of RNAi, which might be involved in the level of post-transcription, translation, genome methylation or conduction of silencing signals, is now making unceasing progress. Clear elucidation of the molecular mechanism could provide important theoretical references and powerful tools for the practical application in this field where RNAi may be put into the use of systematic gene screening, the discovery of new genes and the gene therapy for human tumor or other refractory human diseases.

Animals↗
PubMed2004

RNAi in functional genomics.

There has been a lack of powerful tools for systematic analysis of mammalian gene function, but RNA interference (RNAi) may now provide such a strategy. Stable transcription of RNAi triggers from suitable expression cassettes integrated into the host cell genome by viral gene transfer can induce long-term and heritable gene silencing in mammalian cells. However, the use of RNAi as a genetic tool is limited by difficulties in identifying efficient RNAi triggers, the problem of effective delivery and off-target effects, as well as potential genotoxic side effects of viral gene transfer strategies. Recent insights into the molecular mechanisms of silencing processes mediated by either siRNA or miRNA will allow further optimization of RNAi triggers as genetic tools.

Animals↗
PubMed2004

[Basic research on and application of RNA interference].

RNAi, a novel strategy of gene-silencing induced by dsRNA, has recently become an important topic of discussion. dsRNAs introduced into a living body are processed by an enzyme known as the Dicer and become fractions of 21-23 nt RNAs (siRNA), after which they form protein complexes known as RNA-induced silencing complexes (RISC). The resulting RISC recognizes cognate mRNAs and cleave them. There are 2 ways to introduce dsRNAs to a living body: direct introduction of synthetic dsRNAs, and introduction of DNA templates into cells, followed by production of dsRNAs by transcription. Now that we can apply RNAi technologies into a living body, RNAi has become a widely used tool due to its great simplicity and high efficiency. However, there are still problems to be solved for more efficient use of RNAi. There are a wide range of applications such as analysis of gene functions and gene therapy. It is suggested that small RNAs, called miRNAs, exist in a living body and bind mRNAs to repress their translations. miRNA plays a great role in gene regulation and control of the differentiation and development of cells.

Animals↗
PubMedDate not supplied

A suite of novel human spermatozoal RNAs.

We recently described a complex population of spermatozoal coding RNAs that are delivered to the oocyte on fertilization. These are derived throughout spermatogenesis, representing a record of past events. Recently, evidence has been provided that micro-RNAs are present in testes, suggesting that they might also be carried in ejaculate spermatozoa. To directly test this hypothesis, a unique microarray system capable of directly identifying antisense RNAs and predicted transcripts was utilized. RNA isolated from the ejaculate spermatozoa of 6 normal fertile men was directly hybridized to sense oligonucleotide arrays containing 10,000 elements. This revealed 68 shared RNAs, some of which are similar to those previously defined as micro-RNAs, whereas others were the antisense of previously in silico-predicted transcripts. The results and implications of this study are described in this communication.

Humans↗
PubMed2005

[Research advances on the mechanism of RNA silencing in plants].

RNA silencing is a supervising mechanism in eukaryote which can prevent virus duplication, repress transposition of transposon and regulate gene expression. Compared with that in animals, RNA silencing in plants shows some differences in the function of RdRP, in bi-directional transitive RNAi, and in systemic propagation, etc. Meanwhile,the endogenous small RNAs in plants are more diverse than those in animals. In this paper, it is reviewed of the mechanism of RNA silencing in plants and the possibility of its use in plant functional Genomics.

Gene Expression Regulation, Plant↗
PubMed2005

Small RNAs: classification, biogenesis, and function.

Eukaryotes produce various types of small RNAs of 19-28 nt in length. With rapidly increasing numbers of small RNAs listed in recent years, we have come to realize how widespread their functions are and how diverse the biogenesis pathways have evolved. At the same time, we are beginning to grasp the common features and rules governing the key steps in small RNA pathways. In this review, I will summarize the current classification, biogenesis, action mechanism and function of these fascinating molecules.

Animals↗