| Structural highlights
Function
[NRD1_YEAST] Plays a role in sequence-specific regulation of nuclear pre-mRNA abundance. [PAP2_YEAST] Catalytic subunit of the TRAMP complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism limiting inappropriate expression of genetic information. Polyadenylation is required for the degradative activity of the exosome on several of its nuclear RNA substrates like cryptic transcripts generated by RNA polymerase II and III, or hypomethylated pre-tRNAi-Met. Polyadenylates RNA processing and degradation intermediates of snRNAs, snoRNAs and mRNAs that accumulate in strains lacking a functional exosome. TRF4 is also required for proper nuclear division in mitosis, DNA damage repair and sister chromatid cohesion. Involved in the regulation of histone mRNA levels. May mediate mitotic chromosome condensation.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]
Publication Abstract from PubMed
The Nrd1-Nab3-Sen1 (NNS) complex is essential for controlling pervasive transcription and generating sn/snoRNAs in S. cerevisiae. The NNS complex terminates transcription of noncoding RNA genes and promotes exosome-dependent processing/degradation of the released transcripts. The Trf4-Air2-Mtr4 (TRAMP) complex polyadenylates NNS target RNAs and favors their degradation. NNS-dependent termination and degradation are coupled, but the mechanism underlying this coupling remains enigmatic. Here we provide structural and functional evidence demonstrating that the same domain of Nrd1p interacts with RNA polymerase II and Trf4p in a mutually exclusive manner, thus defining two alternative forms of the NNS complex, one involved in termination and the other in degradation. We show that the Nrd1-Trf4 interaction is required for optimal exosome activity in vivo and for the stimulation of polyadenylation of NNS targets by TRAMP in vitro. We propose that transcription termination and RNA degradation are coordinated by switching between two alternative partners of the NNS complex.
Molecular Basis for Coordinating Transcription Termination with Noncoding RNA Degradation.,Tudek A, Porrua O, Kabzinski T, Lidschreiber M, Kubicek K, Fortova A, Lacroute F, Vanacova S, Cramer P, Stefl R, Libri D Mol Cell. 2014 Aug 7;55(3):467-481. doi: 10.1016/j.molcel.2014.05.031. Epub 2014 , Jul 24. PMID:25066235[18]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
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- ↑ Edwards S, Li CM, Levy DL, Brown J, Snow PM, Campbell JL. Saccharomyces cerevisiae DNA polymerase epsilon and polymerase sigma interact physically and functionally, suggesting a role for polymerase epsilon in sister chromatid cohesion. Mol Cell Biol. 2003 Apr;23(8):2733-48. PMID:12665575
- ↑ Kadaba S, Krueger A, Trice T, Krecic AM, Hinnebusch AG, Anderson J. Nuclear surveillance and degradation of hypomodified initiator tRNAMet in S. cerevisiae. Genes Dev. 2004 Jun 1;18(11):1227-40. Epub 2004 May 14. PMID:15145828 doi:http://dx.doi.org/10.1101/gad.1183804
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- ↑ Egecioglu DE, Henras AK, Chanfreau GF. Contributions of Trf4p- and Trf5p-dependent polyadenylation to the processing and degradative functions of the yeast nuclear exosome. RNA. 2006 Jan;12(1):26-32. PMID:16373491 doi:http://dx.doi.org/10.1261/rna.2207206
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- ↑ Reis CC, Campbell JL. Contribution of Trf4/5 and the nuclear exosome to genome stability through regulation of histone mRNA levels in Saccharomyces cerevisiae. Genetics. 2007 Mar;175(3):993-1010. Epub 2006 Dec 18. PMID:17179095 doi:http://dx.doi.org/genetics.106.065987
- ↑ Hamill S, Wolin SL, Reinisch KM. Structure and function of the polymerase core of TRAMP, a RNA surveillance complex. Proc Natl Acad Sci U S A. 2010 Aug 9. PMID:20696927
- ↑ Tudek A, Porrua O, Kabzinski T, Lidschreiber M, Kubicek K, Fortova A, Lacroute F, Vanacova S, Cramer P, Stefl R, Libri D. Molecular Basis for Coordinating Transcription Termination with Noncoding RNA Degradation. Mol Cell. 2014 Aug 7;55(3):467-481. doi: 10.1016/j.molcel.2014.05.031. Epub 2014 , Jul 24. PMID:25066235 doi:http://dx.doi.org/10.1016/j.molcel.2014.05.031
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