RT Journal A1 Burroughs, A. Maxwell A1 Ando, Yoshinari A1 de Hoon, Michiel J.L. A1 Tomaru, Yasuhiro A1 Nishibu, Takahiro A1 Ukekawa, Ryo A1 Funakoshi, Taku A1 Kurokawa, Tsutomu A1 Suzuki, Harukazu A1 Hayashizaki, Yoshihide A1 Daub, Carsten O. T1 A comprehensive survey of 3′ animal miRNA modification events and a possible role for 3′ adenylation in modulating miRNA targeting effectiveness JF Genome Research JO Genome Research YR 2010 FD October 01 VO 20 IS 10 SP 1398 OP 1410 DO 10.1101/gr.106054.110 UL http://genome.cshlp.org/content/20/10/1398.abstract AB 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.