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SiRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

ABSTRACT: While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent of both Ago and RISC. These siRNAs bind the target messenger RNA at the polyA signal and are capable of redirecting a small amount of polyadenylation to downstream polyA sites when present, however, the majority of the activity appears to be due to inhibition of polyadenylation or deadenylation of the transcript, followed by exosomal degradation of the immature mRNA.

SUBMITTER: Vickers TA

PROVIDER: S-EPMC3401429 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

Vickers Timothy A TA Crooke Stanley T ST

Nucleic acids research 20120315 13

While most siRNAs induce sequence-specific target mRNA cleavage and degradation in a process mediated by Ago2/RNA-induced silencing complex (RISC), certain siRNAs have also been demonstrated to direct target RNA reduction through deadenylation and subsequent degradation of target transcripts in a process which involves Ago1/RISC and P-bodies. In the current study, we present data suggesting that a third class of siRNA exist, which are capable of promoting target RNA reduction that is independent ...[more]

PMID: 22422842

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Project description:BACKGROUND: One of the essential processing events during pre-mRNA maturation is the post-transcriptional addition of a polyadenine [poly(A)] tail. The 3'-end poly(A) track protects mRNA from unregulated degradation, and indicates the integrity of mRNA through recognition by mRNA export and translation machinery. The position of a poly(A) site is predetermined by signals in the pre-mRNA sequence that are recognized by a complex of polyadenylation factors. These signals are generally tri-part sequence patterns around the cleavage site that serves as the future poly(A) site. In plants, there is little sequence conservation among these signal elements, which makes it difficult to develop an accurate algorithm to predict the poly(A) site of a given gene. We attempted to solve this problem. RESULTS: Based on our current working model and the profile of nucleotide sequence distribution of the poly(A) signals and around poly(A) sites in Arabidopsis, we have devised a Generalized Hidden Markov Model based algorithm to predict potential poly(A) sites. The high specificity and sensitivity of the algorithm were demonstrated by testing several datasets, and at the best combinations, both reach 97%. The accuracy of the program, called poly(A) site sleuth or PASS, has been demonstrated by the prediction of many validated poly(A) sites. PASS also predicted the changes of poly(A) site efficiency in poly(A) signal mutants that were constructed and characterized by traditional genetic experiments. The efficacy of PASS was demonstrated by predicting poly(A) sites within long genomic sequences. CONCLUSION: Based on the features of plant poly(A) signals, a computational model was built to effectively predict the poly(A) sites in Arabidopsis genes. The algorithm will be useful in gene annotation because a poly(A) site signifies the end of the transcript. This algorithm can also be used to predict alternative poly(A) sites in known genes, and will be useful in the design of transgenes for crop genetic engineering by predicting and eliminating undesirable poly(A) sites.

Dataset Information

SiRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

Publications

siRNAs targeted to certain polyadenylation sites promote specific, RISC-independent degradation of messenger RNAs.

Similar Datasets

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