MicroRNA家族成員對基因表達的轉錄后調節(jié)有重要作用，參與著很多生物學過程,。大多數(shù)的microRNA是通過Drosha和Dicer的加工得來的,，Drosha將長鏈的原始轉錄本剪切成約含有頸環(huán)結構的65個堿基的microRNA前體，再由Dicer將其加工為含有約22個堿基的雙鏈成熟microRNA,。成熟的microRNA與Argonaute蛋白復合體結合,，通過不完全配對靶向mRNA，阻遏翻譯,。
本文的研究者發(fā)現(xiàn),，microRNA復合體也能靶向非編碼RNA并對其進行調節(jié)。實驗表明,，在秀麗新小桿線蟲中,，Argonaute家族的ALG-1蛋白特異性的結合在microRNAlet-7原始轉錄本的3'端，并調節(jié)下游的生物學事件,。而介導這一過程的正是let-7本身,。進一步研究證明，在人體中,，ALG-1也能與let-7的原始轉錄本結合,。這一研究闡述了一種microRNA新的作用機制，即microRNA除了靶向mRNA調節(jié)翻譯外,，還可以靶向非編碼RNA對自身的表達進行反饋調節(jié),。（生物谷 Bioon.com ）
doi:10.1038/nature11134
PMC:
PMID:
Autoregulation of microRNA biogenesis by let-7 and Argonaute
Dimitrios G. Zisoulis, Zoya S. Kai, Roger K. Chang & Amy E. Pasquinelli.
MicroRNAs (miRNAs) comprise a large family of small RNA molecules that post-transcriptionally regulate gene expression in many biological pathways1. Most miRNAs are derived from long primary transcripts that undergo processing by Drosha to produce ~65-nucleotide precursors that are then cleaved by Dicer, resulting in the mature 22-nucleotide forms2, 3. Serving as guides in Argonaute protein complexes, mature miRNAs use imperfect base pairing to recognize sequences in messenger RNA transcripts, leading to translational repression and destabilization of the target messenger RNAs4, 5. Here we show that the miRNA complex also targets and regulates non-coding RNAs that serve as substrates for the miRNA-processing pathway. We found that the Argonaute protein in Caenorhabditis elegans, ALG-1, binds to a specific site at the 3′ end of let-7 miRNA primary transcripts and promotes downstream processing events. This interaction is mediated by mature let-7 miRNA through a conserved complementary site in its own primary transcript, thus creating a positive-feedback loop. We further show that ALG-1 associates with let-7 primary transcripts in nuclear fractions. Argonaute also binds let-7 primary transcripts in human cells, demonstrating that the miRNA pathway targets non-coding RNAs in addition to protein-coding messenger RNAs across species. Moreover, our studies in C. elegans reveal a novel role for Argonaute in promoting biogenesis of a targeted transcript, expanding the functions of the miRNA pathway in gene regulation. This discovery of autoregulation of let-7 biogenesis establishes a new mechanism for controlling miRNA expression.
