Dual RNA processing roles of Pat1b via cytoplasmic Lsm1-7 and nuclear Lsm2-8 complexes

Pat1 RNA-binding proteins, enriched in processing bodies (P bodies), are key players in cytoplasmic 5′ to 3′ mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nucle...

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Hauptverfasser: Vindry, Caroline (VerfasserIn) , Stoecklin, Georg (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: August 1, 2017
In: Cell reports
Year: 2017, Jahrgang: 20, Heft: 5, Pages: 1187-1200
ISSN:2211-1247
DOI:10.1016/j.celrep.2017.06.091
Online-Zugang:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1016/j.celrep.2017.06.091
Verlag, kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124717309415
Volltext
Verfasserangaben:Caroline Vindry, Aline Marnef, Helen Broomhead, Laure Twyffels, Sevim Ozgur, Georg Stoecklin, Miriam Llorian, Christopher W. Smith, Juan Mata, Dominique Weil, Nancy Standart

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520 |a Pat1 RNA-binding proteins, enriched in processing bodies (P bodies), are key players in cytoplasmic 5′ to 3′ mRNA decay, activating decapping of mRNA in complex with the Lsm1-7 heptamer. Using co-immunoprecipitation and immunofluorescence approaches coupled with RNAi, we provide evidence for a nuclear complex of Pat1b with the Lsm2-8 heptamer, which binds to the spliceosomal U6 small nuclear RNA (snRNA). Furthermore, we establish the set of interactions connecting Pat1b/Lsm2-8/U6 snRNA/SART3 and additional U4/U6.U5 tri-small nuclear ribonucleoprotein particle (tri-snRNP) components in Cajal bodies, the site of snRNP biogenesis. RNA sequencing following Pat1b depletion revealed the preferential upregulation of mRNAs normally found in P bodies and enriched in 3′ UTR AU-rich elements. Changes in >180 alternative splicing events were also observed, characterized by skipping of regulated exons with weak donor sites. Our data demonstrate the dual role of a decapping enhancer in pre-mRNA processing as well as in mRNA decay via distinct nuclear and cytoplasmic Lsm complexes. 
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