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RNA. 2017 Jul;23(7):1035-1047. doi: 10.1261/rna.059808.116. Epub 2017 Apr 11.

DROSHA targets its own transcript to modulate alternative splicing.

Lee D1, Nam JW2, Shin C1,3,4.

Author information

1
Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
2
Department of Life Science, Hanyang University, Seoul 04763, Republic of Korea.
3
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
4
Plant Genomics and Breeding Institute, Seoul National University, Seoul 08826, Republic of Korea.

Abstract

The nuclear RNase III enzyme DROSHA interacts with its cofactor DGCR8 to form the Microprocessor complex, which initiates microRNA (miRNA) maturation by cleaving hairpin structures embedded in primary transcripts. Apart from its central role in the biogenesis of miRNAs, DROSHA is also known to recognize and cleave miRNA-like hairpins in a subset of transcripts without apparent small RNA production. Here, we report that the human DROSHA transcript is one such noncanonical target of DROSHA. Mammalian DROSHA genes have evolved a conserved hairpin structure spanning a specific exon-intron junction, which serves as a substrate for the Microprocessor in human cells but not in murine cells. We show that it is this hairpin element that decides whether the overlapping exon is alternatively or constitutively spliced. We further demonstrate that DROSHA promotes skipping of the overlapping exon in human cells independently of its cleavage function. Our findings add to the expanding list of noncanonical DROSHA functions.

KEYWORDS:

DROSHA; Microprocessor; alternative splicing

PMID:
28400409
PMCID:
PMC5473138
DOI:
10.1261/rna.059808.116
[Indexed for MEDLINE]
Free PMC Article

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