TY - JOUR
T1 - An evolutionarily conserved, alternatively spliced, intron in the p68/DDX5 DEAD-box RNA helicase gene encodes a novel miRNA
AU - Moore, Hayley C.
AU - Johnston, Michael
AU - Nicol, Samantha M.
AU - Bourdon, Jean Christophe
AU - Thompson, Alastair M.
AU - Hutvagner, Gyorgy
AU - Fuller-Pace, Frances V.
PY - 2011/4
Y1 - 2011/4
N2 - The DEAD-box RNA helicase p68 (DDX5) plays important roles in several cellular processes, including transcription, pre-mRNA processing, and microRNA (miRNA) processing. p68 expression is growth and developmentally regulated, and alterations in p68 expression and/or function have been implicated in tumor development. The p68 gene encodes an evolutionarily conserved, alternatively spliced, intron the function of which has to date remained unclear. Although the intron-containing p68 RNA does not appear to yield an alternative p68 protein, it is differentially expressed in cell lines and tissues, indicating regulation of expression. Here we show that the p68 conserved intron encodes a novel putative miRNA, suggesting a previously unknown possible regulatory function for the p68 intron. We show that this miRNA (referred to as p68 miRNA) is processed from the intron via the canonical miRNA-processing pathway and that it associates with the Argonaute protein Ago2. Finally we show that the p68 miRNA suppresses an mRNA bearing complementary target sequences, suggesting that it is functional. These findings suggest a novel mechanism by which alterations in p68 expression may impact on the cell.
AB - The DEAD-box RNA helicase p68 (DDX5) plays important roles in several cellular processes, including transcription, pre-mRNA processing, and microRNA (miRNA) processing. p68 expression is growth and developmentally regulated, and alterations in p68 expression and/or function have been implicated in tumor development. The p68 gene encodes an evolutionarily conserved, alternatively spliced, intron the function of which has to date remained unclear. Although the intron-containing p68 RNA does not appear to yield an alternative p68 protein, it is differentially expressed in cell lines and tissues, indicating regulation of expression. Here we show that the p68 conserved intron encodes a novel putative miRNA, suggesting a previously unknown possible regulatory function for the p68 intron. We show that this miRNA (referred to as p68 miRNA) is processed from the intron via the canonical miRNA-processing pathway and that it associates with the Argonaute protein Ago2. Finally we show that the p68 miRNA suppresses an mRNA bearing complementary target sequences, suggesting that it is functional. These findings suggest a novel mechanism by which alterations in p68 expression may impact on the cell.
KW - Alternatively spliced intron
KW - RNA helicase
KW - miRNA
KW - p68/DDX5
UR - http://www.scopus.com/inward/record.url?scp=79953016022&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953016022&partnerID=8YFLogxK
U2 - 10.1261/rna.2591611
DO - 10.1261/rna.2591611
M3 - Article
C2 - 21346006
AN - SCOPUS:79953016022
SN - 1355-8382
VL - 17
SP - 555
EP - 562
JO - RNA
JF - RNA
IS - 4
ER -