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DROSHA targets its own transcript to modulate alternative splicing

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 recog...

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Detalles Bibliográficos
Autores principales: Lee, Dooyoung, Nam, Jin-Wu, Shin, Chanseok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473138/
https://www.ncbi.nlm.nih.gov/pubmed/28400409
http://dx.doi.org/10.1261/rna.059808.116
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author Lee, Dooyoung
Nam, Jin-Wu
Shin, Chanseok
author_facet Lee, Dooyoung
Nam, Jin-Wu
Shin, Chanseok
author_sort Lee, Dooyoung
collection PubMed
description 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.
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spelling pubmed-54731382018-07-01 DROSHA targets its own transcript to modulate alternative splicing Lee, Dooyoung Nam, Jin-Wu Shin, Chanseok RNA Report 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. Cold Spring Harbor Laboratory Press 2017-07 /pmc/articles/PMC5473138/ /pubmed/28400409 http://dx.doi.org/10.1261/rna.059808.116 Text en © 2017 Lee et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Report
Lee, Dooyoung
Nam, Jin-Wu
Shin, Chanseok
DROSHA targets its own transcript to modulate alternative splicing
title DROSHA targets its own transcript to modulate alternative splicing
title_full DROSHA targets its own transcript to modulate alternative splicing
title_fullStr DROSHA targets its own transcript to modulate alternative splicing
title_full_unstemmed DROSHA targets its own transcript to modulate alternative splicing
title_short DROSHA targets its own transcript to modulate alternative splicing
title_sort drosha targets its own transcript to modulate alternative splicing
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473138/
https://www.ncbi.nlm.nih.gov/pubmed/28400409
http://dx.doi.org/10.1261/rna.059808.116
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