A comprehensive survey of 3′ animal miRNA modification events and a possible role for 3′ adenylation in modulating miRNA targeting effectiveness

被引：273

作者：

Burroughs, A. Maxwell ^{[1
]}

Ando, Yoshinari ^{[1
]}

de Hoon, Michiel J. L. ^{[1
]}

Tomaru, Yasuhiro ^{[1
,2
]}

Nishibu, Takahiro ^{[3
]}

Ukekawa, Ryo ^{[3
]}

Funakoshi, Taku ^{[3
]}

Kurokawa, Tsutomu ^{[3
]}

Suzuki, Harukazu ^{[1
]}

Hayashizaki, Yoshihide ^{[1
,2
]}

Daub, Carsten O. ^{[1
]}

机构：

[1] RIKEN Yokohama Inst, OSC, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[2] Yokohama City Univ, Int Grad Sch Arts & Sci, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[3] Wako Pure Chem Ind Ltd, Chuo Ku, Osaka 5408605, Japan

来源：

GENOME RESEARCH | 2010年 / 20卷 / 10期

关键词：

CYTOPLASMIC POLY(A) POLYMERASE; EMBRYONIC STEM-CELLS; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTOR; MICRORNAS; RNA; EXPRESSION; FAMILY; POLYADENYLATION; IDENTIFICATION;

D O I：

10.1101/gr.106054.110

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Animal microRNA sequences are subject to 3' nucleotide addition. Through detailed analysis of deep-sequenced short RNA data sets, we show adenylation and uridylation of miRNA is globally present and conserved across Drosophila and vertebrates. To better understand 3' adenylation function, we deep-sequenced RNA after knockdown of nucleotidyltransferase enzymes. The PAPD4 nucleotidyltransferase adenylates a wide range of miRNA loci, but adenylation does not appear to affect miRNA stability on a genome-wide scale. Adenine addition appears to reduce effectiveness of miRNA targeting of mRNA transcripts while deep-sequencing of RNA bound to immunoprecipitated Argonaute (AGO) subfamily proteins EIF2C1-EIF2C3 revealed substantial reduction of adenine addition in miRNA associated with EIF2C2 and EIF2C3. Our findings show 3' addition events are widespread and conserved across animals, PAPD4 is a primary miRNA adenylating enzyme, and suggest a role for 3' adenine addition in modulating miRNA effectiveness, possibly through interfering with incorporation into the RNA-induced silencing complex (RISC), a regulatory role that would complement the role of miRNA uridylation in blocking DICER1 uptake.

引用

页码：1398 / 1410

页数：13

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