PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

• DOI: 10.1073/pnas.1317751111
• Publication Date: 2014-07-22T00:59:36Z
• Authors: Joost Boele; Helena Persson; Jay W. Shin; Yuri Ishizu; Inga S. Newie; Rolf Søkilde; Shannon M. Hawkins; Cristian Coarfa; Kazuhiro Ikeda; Ken-ichi Takayama; Kuniko Horie-Inoue; Yoshinari Ando; A. Maxwell Burroughs; Chihiro Sasaki; Chizuru Suzuki; Mizuho Sakai; Shintaro Aoki; Ayumi Ogawa; Akira Hasegawa; Marina Lizio; Kaoru Kaida; Bas Teusink; Piero Carninci; Harukazu Suzuki; Satoshi Inoue; Preethi H. Gunaratne; Carlos Rovira; Yoshihide Hayashi...; Michiel J. L. de ...
• Keywords: Adenylylation; Exoribonuclease

Next-generation sequencing experiments have shown that microRNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found mature miR-21, the most widely researched miRNA because of its importance human disease, produced two prevalent isomiR forms differ by 1 nt at their 3' end, and moreover end miR-21 posttranscriptionally adenylated noncanonical poly(A) polymerase PAPD5. PAPD5 knockdown caused an increase expression level, suggesting PAPD5-mediated adenylation leads to degradation. Exoribonuclease followed small-RNA suggested PARN degrades 3'-to-5' direction. In accordance with this model, microarray profiling demonstrated results a down-regulation target mRNAs. disruption degradation pathway general feature tumors across wide range tissues, as evidenced data from The Cancer Genome Atlas, well noncancerous proliferative disease psoriasis. conclude mediate oncogenic through tailing trimming process, disrupted cancer other diseases.