KSRP-PMR1-exosome association determines parathyroid hormone mRNA levels and stability in transfected cells

Morris Nechama, Yong Peng, Osnat Bell, Paola Briata, Roberto Gherzi, Daniel R. Schoenberg, Tally Naveh-Many

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Parathyroid hormone (PTH) gene expression is regulated post-transcriptionally through the binding of the trans-acting proteins AU rich binding factor 1 (AUF1), Upstream of N-ras (Unr) and KH-type splicing regulatory protein (KSRP) to an AU rich element (ARE) in PTH mRNA 3'-UTR. AUF1 and Unr stabilize PTH mRNA while KSRP, recruiting the exoribonucleolytic complex exosome, promotes PTH mRNA decay. Results: PTH mRNA is cleaved by the endoribonuclease polysomal ribonuclease 1 (PMR1) in an ARE-dependent manner. Moreover, PMR1 co-immunoprecipitates with PTH mRNA, the exosome and KSRP. Knock-down of either exosome components or KSRP by siRNAs prevents PMR1-mediated cleavage of PTH mRNA. Conclusion: PTH mRNA is a target for the endonuclease PMR1. The PMR1 mediated decrease in PTH mRNA levels involves the PTH mRNA 3'-UTR ARE, KSRP and the exosome. This represents an unanticipated mechanism by which the decay of an ARE-containing mRNA is facilitated by KSRP and is dependent on both the exosome and an endoribonuclease.

Original languageEnglish
Article number1471
Pages (from-to)70
Number of pages1
JournalBMC Cell Biology
Volume10
DOIs
Publication statusPublished - Sep 23 2009

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Protein Splicing
Exosomes
RNA Stability
Ribonucleases
Parathyroid Hormone
AU Rich Elements
Messenger RNA
Endoribonucleases
3' Untranslated Regions
Endonucleases

ASJC Scopus subject areas

  • Cell Biology

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KSRP-PMR1-exosome association determines parathyroid hormone mRNA levels and stability in transfected cells. / Nechama, Morris; Peng, Yong; Bell, Osnat; Briata, Paola; Gherzi, Roberto; Schoenberg, Daniel R.; Naveh-Many, Tally.

In: BMC Cell Biology, Vol. 10, 1471, 23.09.2009, p. 70.

Research output: Contribution to journalArticle

Nechama, Morris ; Peng, Yong ; Bell, Osnat ; Briata, Paola ; Gherzi, Roberto ; Schoenberg, Daniel R. ; Naveh-Many, Tally. / KSRP-PMR1-exosome association determines parathyroid hormone mRNA levels and stability in transfected cells. In: BMC Cell Biology. 2009 ; Vol. 10. pp. 70.
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