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PAPD5-mediated 3' a...
PAPD5-mediated 3' adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease.
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Boele, Joost (author)
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- Persson, Helena (author)
- Karolinska Institutet
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Shin, Jay W (author)
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Ishizu, Yuri (author)
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- Newie, Inga (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Sökilde, Rolf (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Hawkins, Shannon M (author)
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Coarfa, Cristian (author)
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Ikeda, Kazuhiro (author)
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Takayama, Ken-Ichi (author)
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Horie-Inoue, Kuniko (author)
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Ando, Yoshinari (author)
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Burroughs, A Maxwell (author)
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Sasaki, Chihiro (author)
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Suzuki, Chizuru (author)
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Sakai, Mizuho (author)
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Aoki, Shintaro (author)
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Ogawa, Ayumi (author)
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Hasegawa, Akira (author)
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Lizio, Marina (author)
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Kaida, Kaoru (author)
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Teusink, Bas (author)
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Carninci, Piero (author)
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Suzuki, Harukazu (author)
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Inoue, Satoshi (author)
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Gunaratne, Preethi H (author)
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- Rovira, Carlos (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Hayashizaki, Yoshihide (author)
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de Hoon, Michiel J L (author)
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(creator_code:org_t)
- 2014-07-21
- 2014
- English.
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In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:31, s. 11467-11472
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Abstract
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- Next-generation sequencing experiments have shown that microRNAs (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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Boele, Joost
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Persson, Helena
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Shin, Jay W
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Ishizu, Yuri
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Newie, Inga
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Sökilde, Rolf
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show more...
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Hawkins, Shannon ...
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Coarfa, Cristian
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Ikeda, Kazuhiro
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Takayama, Ken-Ic ...
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Horie-Inoue, Kun ...
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Ando, Yoshinari
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Burroughs, A Max ...
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Sasaki, Chihiro
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Suzuki, Chizuru
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Sakai, Mizuho
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Aoki, Shintaro
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Ogawa, Ayumi
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Hasegawa, Akira
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Lizio, Marina
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Kaida, Kaoru
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Teusink, Bas
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Carninci, Piero
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Suzuki, Harukazu
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Inoue, Satoshi
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Gunaratne, Preet ...
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Rovira, Carlos
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Hayashizaki, Yos ...
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de Hoon, Michiel ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Proceedings of t ...
- By the university
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Lund University
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Karolinska Institutet