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


RESULTS
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
Thus, alternative Drosha processing might be a novel mechanism for diversification of the miRNA target gene pool.
Center of Excellence in Infectious Disease Research, Department of Biomedical Sciences, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas, United States of America. haoquan.wu@ttuhsc.edu
Haoquan
H
Wu
Chunting
C
Ye
Danielle
D
Ramirez
N
N
Manjunath
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D043244:Ribonuclease III / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D013816:Thermodynamics
D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; C513400:Drosha protein, mouse; D043244:Ribonuclease III