An unsolved mystery: The target-recognizing RNA species of microRNA genes

被引:9
作者
Chen, Chang-Zheng [1 ,2 ]
机构
[1] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Baxter Lab Stem Cell Biol, Stanford, CA 94305 USA
关键词
MicroRNA; Antisense regulatory RNA microRNA; Primary microRNA; Precursor microRNA; Mature microRNA; Target recognition; COLE1 PLASMID REPLICATION; DOUBLE-STRANDED-RNA; LOOP NUCLEOTIDES CONTROL; MESSENGER-RNA; ANTISENSE RNA; PRIMER TRANSCRIPT; OXYS RNA; BINDING; BIOGENESIS; LET-7;
D O I
10.1016/j.biochi.2013.05.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNAs (miRNAs) are an abundant class of endogenous similar to 21-nucleotide (nt) RNAs. These small RNAs are produced from long primary miRNA transcripts - pri-miRNAs - through sequential endonucleolytic maturation steps that yield precursor miRNA (pre-miRNA) intermediates and then the mature miRNAs. The mature miRNAs are loaded into the RNA-induced silencing complexes (RISC), and guide RISC to target mRNAs for cleavage and/or translational repression. This paradigm, which represents one of major discoveries of modern molecular biology, is built on the assumption that mature miRNAs are the only species produced from miRNA genes that recognize targets. This assumption has guided the miRNA field for more than a decade and has led to our current understanding of the mechanisms of target recognition and repression by miRNAs. Although progress has been made, fundamental questions remain unanswered with regard to the principles of target recognition and mechanisms of repression. Here I raise questions about the assumption that mature miRNAs are the only target-recognizing species produced from miRNA genes and discuss the consequences of working under an incomplete or incorrect assumption. Moreover, I present evolution-based and experimental evidence that support the roles of pri-/pre-miRNAs in target recognition and repression. Finally, I propose a conceptual framework that integrates the functions of pri-/pre-miRNAs and mature miRNAs in target recognition and repression. The integrated framework opens experimental enquiry and permits interpretation of fundamental problems that have so far been precluded. (C) 2013 The Author. Published by Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:1663 / 1676
页数:14
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