Profiling of T helper cell-derived small RNAs reveals unique antisense transcripts and differential association of miRNAs with argonaute proteins 1 and 2.

Profiling of T helper cell-derived small RNAs reveals unique antisense transcripts and differential association of miRNAs with argonaute proteins 1 and 2.
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DOI:
10.1093/nar/gks1098
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发表时间:
2013-01
影响因子:
14.9
通讯作者:
Corry DB
Corry DB
中科院分区:
生物学2区
文献类型:
--
作者:
Polikepahad S;Corry DB

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RNA interference mediated through antisense transcripts is a fundamentally important mechanism regulating gene expression that remains incompletely understood. Here, we have used next-generation sequencing to determine from mouse CD4+ T cells the functional implications of antisense transcripts binding to argonaute (AGO) proteins that mediate RNA interference and post-transcriptional gene silencing. This effort identified 90 new microRNAs (miRNAs) and six endogenous hairpin RNA-derived small interfering RNAs (siRNAs) mapping to distinct introns. Unexpectedly, 69 miRNAs were expressed as non-canonical isomiRs as the dominant AGO-binding transcript, with extensive 3′ terminal nucleotide modifications. Furthermore, differential expression analysis between AGO1- and AGO2-bound miRNAs suggested preferential binding of isomiRs ending with 3′ adenine residues to AGO1 and 3′ uridine residues to AGO2. Analysis of the putative targets of all miRNAs suggested a striking preference for regulating transcription and transcription factors with additional evidence of a functional division of labor between AGO proteins in this regard. We further provide evidence that multiple mitochondrial genomic loci serve as the source of endogenous cis-natural antisense transcripts. These findings imply diversity in AGO protein function based on differential miRNA binding and indicate that RNA interference-based gene regulation is more complex than previously recognized.
DOI: 10.1002/0471250953.bi1107s32
发表时间: 2010-12
影响因子: --
作者:
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影响因子: 4.4
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发表时间: 2004-05-01
期刊: PEDIATRIC RESEARCH
影响因子: 3.6
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通讯作者: Comi, GP