Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.

It is generally believed that the miRNA processing machinery ensures the generation of a mature miRNA with a fixed sequence, particularly at its 5' end. However, we and others have recently noted that the ends of a given mature miRNA are not absolutely fixed, but subject to variation. Neither t...

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Main Authors: Haoquan Wu, Chunting Ye, Danielle Ramirez, N Manjunath
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-10-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2762519?pdf=render
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author Haoquan Wu
Chunting Ye
Danielle Ramirez
N Manjunath
author_facet Haoquan Wu
Chunting Ye
Danielle Ramirez
N Manjunath
author_sort Haoquan Wu
collection DOAJ
description It is generally believed that the miRNA processing machinery ensures the generation of a mature miRNA with a fixed sequence, particularly at its 5' end. However, we and others have recently noted that the ends of a given mature miRNA are not absolutely fixed, but subject to variation. Neither the significance nor the mechanism behind the generation of such miRNA polymorphism is understood. miR-142 is an abundantly expressed miRNA in hematopoietic cells and exhibits a high frequency of 5' end polymorphism.Here we show that a shift in the Drosha processing of pri-miRNA generates multiple forms of miR-142s in vivo with differing 5' ends that might target different genes. Sequence analysis of several pre-miRNA ends cloned from T cells reveals that unlike many other pri-miRNAs that are processed into a single pre-miRNA, pri-miR-142 is processed into 3 distinct pre-miR-142s. Dicer processing studies suggest that each of the 3 pre-miR-142s is processed into a distinct double-stranded miRNA, giving rise to 4 mature miRNA variants that might regulate different target gene pools.Thus, alternative Drosha processing might be a novel mechanism for diversification of the miRNA target gene pool.
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spelling doaj.art-87ecc0a08d5a4a86b1b6076050067cc22022-12-22T03:15:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e756610.1371/journal.pone.0007566Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.Haoquan WuChunting YeDanielle RamirezN ManjunathIt is generally believed that the miRNA processing machinery ensures the generation of a mature miRNA with a fixed sequence, particularly at its 5' end. However, we and others have recently noted that the ends of a given mature miRNA are not absolutely fixed, but subject to variation. Neither the significance nor the mechanism behind the generation of such miRNA polymorphism is understood. miR-142 is an abundantly expressed miRNA in hematopoietic cells and exhibits a high frequency of 5' end polymorphism.Here we show that a shift in the Drosha processing of pri-miRNA generates multiple forms of miR-142s in vivo with differing 5' ends that might target different genes. Sequence analysis of several pre-miRNA ends cloned from T cells reveals that unlike many other pri-miRNAs that are processed into a single pre-miRNA, pri-miR-142 is processed into 3 distinct pre-miR-142s. Dicer processing studies suggest that each of the 3 pre-miR-142s is processed into a distinct double-stranded miRNA, giving rise to 4 mature miRNA variants that might regulate different target gene pools.Thus, alternative Drosha processing might be a novel mechanism for diversification of the miRNA target gene pool.http://europepmc.org/articles/PMC2762519?pdf=render
spellingShingle Haoquan Wu
Chunting Ye
Danielle Ramirez
N Manjunath
Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.
PLoS ONE
title Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.
title_full Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.
title_fullStr Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.
title_full_unstemmed Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.
title_short Alternative processing of primary microRNA transcripts by Drosha generates 5' end variation of mature microRNA.
title_sort alternative processing of primary microrna transcripts by drosha generates 5 end variation of mature microrna
url http://europepmc.org/articles/PMC2762519?pdf=render
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AT danielleramirez alternativeprocessingofprimarymicrornatranscriptsbydroshagenerates5endvariationofmaturemicrorna
AT nmanjunath alternativeprocessingofprimarymicrornatranscriptsbydroshagenerates5endvariationofmaturemicrorna