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


ABSTRACT:

Background

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.

Methodology/principal findings

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.

Conclusions/significance

Thus, alternative Drosha processing might be a novel mechanism for diversification of the miRNA target gene pool.

SUBMITTER: Wu H 

PROVIDER: S-EPMC2762519 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Wu Haoquan H   Ye Chunting C   Ramirez Danielle D   Manjunath N N  

PloS one 20091027 10


<h4>Background</h4>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 freq  ...[more]

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