Human Disease

Management

Small RNA

IsomiR Bank

Paper Link:

http://www.ncbi.nlm.nih.gov/pubmed/27153728

Website:

http://mcg.ustc.edu.cn/bsc/isomir/

Introduction

MicroRNAs (miRNAs), with average length of 22 nucleotides, are ubiquitously expressed and regulate many essential biological processes mainly via post-transcriptional silencing of genes through mRNA decay and/or translational repression (Bartel, 2004). During this process, the primary miRNA transcripts (pri-miRNAs) are mainly cleaved by complexes of RNAses III (Drosha and DGCR8) and give rise to one or more precursor miRNAs (pre-miRNAs) hairpins. Following Dicer processing, the hairpins release short double-stranded RNA. One of the resultant strand (defined as mature miRNA) binds to the protein Argonaut 2 (Ago2), and gets incorporated into the RNA Induced Silencing Complexes (RISCs). It guides RISCs to the 3’UTR of mRNAs by base pairing with fully or partially complementary sequences (Griffiths-Jones, et al., 2006). Previously, miRNAs were only annotated as the canonical sequences. However, extensive application of high-throughput sequencing technology to detect expression profile of miRNA has revealed that miRNAs can frequently exhibit differences from their corresponding canonical mature sequences, generating multiple variants known as isoforms of miRNAs (isomiRs) (Guo and Lu, 2010; Li, et al., 2012; Llorens, et al., 2013; Vaz, et al., 2013; Wang, et al., 2008). Generally, the reference miRBase miRNA (having the canonical sequence) often differs from the most abundant isomiR (Ameres and Zamore, 2013; Loher, et al., 2014). There are two main processes that lead to the production of isomiRs. These isomiRs mainly originate via the imprecise and alternative cleavage (not completely random) during the pre-miRNA processing and post-transcriptional modifications that have influence on miRNA stability, their sub-cellular localization and target selection (Ameres and Zamore, 2013; Loher, et al.,2014). On the other hand, miRNA editing is the process that generates isomiRs by post-transcriptional enzymatic editing of the miRNA genome (Ameres and Zamore, 2013; Neilsen, et al., 2012). It has also been reported recently that isomiRs can significantly affect the half-life of miRNA, as well as their sub-cellular localization and their target specification (Ameres and Zamore, 2013; Cloonan, et al., 2011; Li, et al., 2012; Wang, et al.,2008).

Here, we have established a database, IsomiR Bank, to support and facilitate the ongoingisomiRs research. Our database contains 308,919 isomiRs detected from 2,727 samples (Small RNA NGS data downloaded from ArrayExpress database) of eight species (Arabidopsis thaliana, Drosophila melanogaster, Danio rerio, Homo sapiens, Mus musculus, Oryza sativa, Solanum lycopersicum and Zea mays) with manually curated metadata for each sample (organism, sex, tissue, development stage, age, experiment condition, treatment and sequencing platform). IsomiR Bank also has a user-friendly web interface allowing researchers to quickly find and navigate the isomiRs of their interest and related annotation along with the functional analysis that can help in evaluating the effects of isomiR on target selection and downstream pathways. Our database is not only a collection of isomiRs from NGS data but also a tool to find out the candidate functional isomiRs for further experimental studies.

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