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

Joost Boele, Helena Persson, Jay W. Shin, Yuri Ishizu, Inga S. Newie, Rolf Søkilde, Shannon 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 LizioKaoru Kaida, Bas Teusink, Piero Carninci, Harukazu Suzuki, Satoshi Inoue, Preethi H. Gunaratne, Carlos Rovira, Yoshihide Hayashizaki, Michiel J L De Hoon

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)11467-11472
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number31
DOIs
StatePublished - Aug 5 2014
Externally publishedYes

Fingerprint

MicroRNAs
Exoribonucleases
Polynucleotide Adenylyltransferase
RNA Sequence Analysis
Neoplasms
Atlases
Psoriasis
Protein Isoforms
Down-Regulation
Genome
Messenger RNA

Keywords

  • microRNA processing
  • Nucleotidyl transferase

ASJC Scopus subject areas

  • General

Cite this

PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease. / Boele, Joost; Persson, Helena; Shin, Jay W.; Ishizu, Yuri; Newie, Inga S.; Søkilde, Rolf; Hawkins, Shannon; Coarfa, Cristian; Ikeda, Kazuhiro; Takayama, Ken Ichi; Horie-Inoue, Kuniko; Ando, Yoshinari; Burroughs, A. Maxwell; Sasaki, Chihiro; Suzuki, Chizuru; Sakai, Mizuho; Aoki, Shintaro; Ogawa, Ayumi; Hasegawa, Akira; Lizio, Marina; Kaida, Kaoru; Teusink, Bas; Carninci, Piero; Suzuki, Harukazu; Inoue, Satoshi; Gunaratne, Preethi H.; Rovira, Carlos; Hayashizaki, Yoshihide; De Hoon, Michiel J L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 31, 05.08.2014, p. 11467-11472.

Research output: Contribution to journalArticle

Boele, J, Persson, H, Shin, JW, Ishizu, Y, Newie, IS, Søkilde, R, Hawkins, S, Coarfa, C, Ikeda, K, Takayama, KI, Horie-Inoue, K, Ando, Y, Burroughs, AM, Sasaki, C, Suzuki, C, Sakai, M, Aoki, S, Ogawa, A, Hasegawa, A, Lizio, M, Kaida, K, Teusink, B, Carninci, P, Suzuki, H, Inoue, S, Gunaratne, PH, Rovira, C, Hayashizaki, Y & De Hoon, MJL 2014, 'PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 31, pp. 11467-11472. https://doi.org/10.1073/pnas.1317751111
Boele, Joost ; Persson, Helena ; Shin, Jay W. ; Ishizu, Yuri ; Newie, Inga S. ; Søkilde, Rolf ; Hawkins, Shannon ; Coarfa, Cristian ; Ikeda, Kazuhiro ; Takayama, Ken Ichi ; Horie-Inoue, Kuniko ; Ando, Yoshinari ; Burroughs, A. Maxwell ; Sasaki, Chihiro ; Suzuki, Chizuru ; Sakai, Mizuho ; Aoki, Shintaro ; Ogawa, Ayumi ; Hasegawa, Akira ; Lizio, Marina ; Kaida, Kaoru ; Teusink, Bas ; Carninci, Piero ; Suzuki, Harukazu ; Inoue, Satoshi ; Gunaratne, Preethi H. ; Rovira, Carlos ; Hayashizaki, Yoshihide ; De Hoon, Michiel J L. / PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 31. pp. 11467-11472.
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T1 - PAPD5-mediated 3′ adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease

AU - Boele, Joost

AU - Persson, Helena

AU - Shin, Jay W.

AU - Ishizu, Yuri

AU - Newie, Inga S.

AU - Søkilde, Rolf

AU - Hawkins, Shannon

AU - Coarfa, Cristian

AU - Ikeda, Kazuhiro

AU - Takayama, Ken Ichi

AU - Horie-Inoue, Kuniko

AU - Ando, Yoshinari

AU - Burroughs, A. Maxwell

AU - Sasaki, Chihiro

AU - Suzuki, Chizuru

AU - Sakai, Mizuho

AU - Aoki, Shintaro

AU - Ogawa, Ayumi

AU - Hasegawa, Akira

AU - Lizio, Marina

AU - Kaida, Kaoru

AU - Teusink, Bas

AU - Carninci, Piero

AU - Suzuki, Harukazu

AU - Inoue, Satoshi

AU - Gunaratne, Preethi H.

AU - Rovira, Carlos

AU - Hayashizaki, Yoshihide

AU - De Hoon, Michiel J L

PY - 2014/8/5

Y1 - 2014/8/5

N2 - Next-generation sequencing experiments have shown that micro-RNAs (miRNAs) are expressed in many different isoforms (isomiRs), whose biological relevance is often unclear. We found that mature miR-21, the most widely researched miRNA because of its importance in human disease, is produced in two prevalent isomiR forms that differ by 1 nt at their 3′ end, and moreover that the 3? end of miR-21 is posttranscriptionally adenylated by the noncanonical poly(A) polymerase PAPD5. PAPD5 knockdown caused an increase in the miR-21 expression level, suggesting that PAPD5-mediated adenylation of miR-21 leads to its degradation. Exoribonuclease knockdown experiments followed by small-RNA sequencing suggested that PARN degrades miR-21 in the 3′-to-5′ direction. In accordance with this model, microarray expression profiling demonstrated that PAPD5 knockdown results in a down-regulation of miR-21 target mRNAs. We found that disruption of the miR-21 adenylation and degradation pathway is a general feature in tumors across a wide range of tissues, as evidenced by data from The Cancer Genome Atlas, as well as in the noncancerous proliferative disease psoriasis. We conclude that PAPD5 and PARN mediate degradation of oncogenic miRNA miR-21 through a tailing and trimming process, and that this pathway is disrupted in cancer and other proliferative diseases.

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KW - microRNA processing

KW - Nucleotidyl transferase

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