Lower and upper stem-single-stranded RNA junctions together determine the Drosha cleavage site.

Abstract:

:Microprocessor [Drosha-DGCR8 (DiGeorge syndrome critical region gene 8) complex] processing of primary microRNA (pri-miRNA) is the critical first step in miRNA biogenesis, but how the Drosha cleavage site is determined has been unclear. Previous models proposed that the Drosha-DGCR8 complex measures either ~22 nt from the upper stem-single-stranded RNA (ssRNA, terminal loop) junction or ~11 nt from the lower stem-ssRNA junction to determine the cleavage site. Here, using miRNA-offset RNAs to determine the Drosha cleavage site, we show that the Microprocessor measures the distances from both the lower and upper stem-ssRNA junctions to determine the cleavage site in human cells, and optimal distances from both structures are critical to the precision of Drosha processing. If the distances are not optimal, Drosha tends to cleave at multiple sites, which can, in turn, generate multiple 5' isomiRs. Thus, our results also reveal a mechanism of 5' isomiR generation.

authors

Ma H,Wu Y,Choi JG,Wu H

doi

10.1073/pnas.1311639110

subject

Has Abstract

pub_date

2013-12-17 00:00:00

pages

20687-92

issue

51

eissn

0027-8424

issn

1091-6490

pii

1311639110

journal_volume

110

pub_type

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