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

Hongming Ma, Yonggan Wu, Jang Gi Choi, Haoquan Wu

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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 stem̈Csingle-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 CssRNA 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.

Original languageEnglish
Pages (from-to)20687-20692
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number51
DOIs
StatePublished - Dec 17 2013

Keywords

  • Alternative Drosha processing
  • DcRNA
  • MoR

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