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The potential functions of primary microRNAs in target recognition and repression
Author(s) -
Trujillo Robin Deis,
Yue SiBiao,
Tang Yujie,
O'Gorman William E,
Chen ChangZheng
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.208
Subject(s) - biology , microrna , psychological repression , function (biology) , gene , rna , computational biology , regulation of gene expression , genetics , rna interference , gene expression , microbiology and biotechnology
Major RNA products of a microRNA (miRNA) gene—the long primary transcript (pri‐miRNA), the ∼70‐nucleotide (nt) precursor miRNA (pre‐miRNA), and the ∼21‐nt mature miRNA—all contain the same sequence required for target gene recognition. Thus, it is intrinsically difficult to discern the contribution of individual RNA species or to rule out a function of miRNA precursor species in target repression. Here, we describe a novel approach to dissect the functional contribution of pri‐miRNA without compromising important cellular pathways. We show that pri‐let‐7 has a direct function in target repression in the absence of properly processed mature let‐7. Moreover, we show that loop nucleotides provide regulatory controls of the activity of pri‐let‐7 by modulating interactions between pri‐let‐7 and target RNAs in vitro and in vivo . Finally, we show that human let‐7a‐3 pri‐miRNA can directly interact with target mRNAs. These findings illustrate that the regulatory information encoded in structured pri‐miRNAs may be translated into function through direct interactions with target mRNAs.