The Structure of Transcription Termination Factor Nrd1 Reveals an Original Mode for GUAA Recognition

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2017 Oct 4

PMID 28973465

Citations 5

Authors

Elsa Franco-Echevarria

Noelia Gonzalez-Polo

Silvia Zorrilla

Santiago Martinez-Lumbreras

Clara M Santiveri

Ramon Campos-Olivas

Mar Sanchez

Olga Calvo

Beatriz Gonzalez

Jose Manuel Perez-Canadillas

Affiliations

Soon will be listed here.

Abstract

Transcription termination of non-coding RNAs is regulated in yeast by a complex of three RNA binding proteins: Nrd1, Nab3 and Sen1. Nrd1 is central in this process by interacting with Rbp1 of RNA polymerase II, Trf4 of TRAMP and GUAA/G terminator sequences. We lack structural data for the last of these binding events. We determined the structures of Nrd1 RNA binding domain and its complexes with three GUAA-containing RNAs, characterized RNA binding energetics and tested rationally designed mutants in vivo. The Nrd1 structure shows an RRM domain fused with a second α/β domain that we name split domain (SD), because it is formed by two non-consecutive segments at each side of the RRM. The GUAA interacts with both domains and with a pocket of water molecules, trapped between the two stacking adenines and the SD. Comprehensive binding studies demonstrate for the first time that Nrd1 has a slight preference for GUAA over GUAG and genetic and functional studies suggest that Nrd1 RNA binding domain might play further roles in non-coding RNAs transcription termination.

Citing Articles

Overexpression of the RNA-binding protein NrdA affects global gene expression and secondary metabolism in species.

Kadooka C, Izumitsu K, Asai T, Hiramatsu K, Mori K, Okutsu K mSphere. 2025; 10(2):e0084924.

PMID: 39853104 PMC: 11852746. DOI: 10.1128/msphere.00849-24.

The Nrd1-Nab3-Sen1 transcription termination complex from a structural perspective.

Chaves-Arquero B, Perez-Canadillas J Biochem Soc Trans. 2023; 51(3):1257-1269.

PMID: 37222282 PMC: 10317158. DOI: 10.1042/BST20221418.

A Genome-Wide Screen Reveals That Endocytic Genes Are Important for Pma1p Asymmetry during Cell Division in .

Yoon S, Jang E, Ko N, Kim M, Kim S, Moon Y Int J Mol Sci. 2022; 23(4).

PMID: 35216480 PMC: 8874555. DOI: 10.3390/ijms23042364.

Structural basis of Nrd1-Nab3 heterodimerization.

Chaves-Arquero B, Martinez-Lumbreras S, Camero S, Santiveri C, Mirassou Y, Campos-Olivas R Life Sci Alliance. 2022; 5(4).

PMID: 35022249 PMC: 8761494. DOI: 10.26508/lsa.202101252.

Genetic screen for suppression of transcriptional interference identifies a gain-of-function mutation in Pol2 termination factor Seb1.

Schwer B, Garg A, Jacewicz A, Shuman S Proc Natl Acad Sci U S A. 2021; 118(33).

PMID: 34389684 PMC: 8379984. DOI: 10.1073/pnas.2108105118.

References

Schulz D, Schwalb B, Kiesel A, Baejen C, Torkler P, Gagneur J . Transcriptome surveillance by selective termination of noncoding RNA synthesis. Cell. 2013; 155(5):1075-87. DOI: 10.1016/j.cell.2013.10.024. View

Vasiljeva L, Kim M, Mutschler H, Buratowski S, Meinhart A . The Nrd1-Nab3-Sen1 termination complex interacts with the Ser5-phosphorylated RNA polymerase II C-terminal domain. Nat Struct Mol Biol. 2008; 15(8):795-804. PMC: 2597375. DOI: 10.1038/nsmb.1468. View

Kim M, Vasiljeva L, Rando O, Zhelkovsky A, Moore C, Buratowski S . Distinct pathways for snoRNA and mRNA termination. Mol Cell. 2006; 24(5):723-734. DOI: 10.1016/j.molcel.2006.11.011. View

Santiveri C, Mirassou Y, Rico-Lastres P, Martinez-Lumbreras S, Perez-Canadillas J . Pub1p C-terminal RRM domain interacts with Tif4631p through a conserved region neighbouring the Pab1p binding site. PLoS One. 2011; 6(9):e24481. PMC: 3169606. DOI: 10.1371/journal.pone.0024481. View

Tudek A, Porrua O, Kabzinski T, Lidschreiber M, Kubicek K, Fortova A . Molecular basis for coordinating transcription termination with noncoding RNA degradation. Mol Cell. 2014; 55(3):467-81. PMC: 4186968. DOI: 10.1016/j.molcel.2014.05.031. View

Thiebaut M, Kisseleva-Romanova E, Rougemaille M, Boulay J, Libri D . Transcription termination and nuclear degradation of cryptic unstable transcripts: a role for the nrd1-nab3 pathway in genome surveillance. Mol Cell. 2006; 23(6):853-64. DOI: 10.1016/j.molcel.2006.07.029. View

Emsley P, Lohkamp B, Scott W, Cowtan K . Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 4):486-501. PMC: 2852313. DOI: 10.1107/S0907444910007493. View

Runner V, Podolny V, Buratowski S . The Rpb4 subunit of RNA polymerase II contributes to cotranscriptional recruitment of 3' processing factors. Mol Cell Biol. 2008; 28(6):1883-91. PMC: 2268395. DOI: 10.1128/MCB.01714-07. View

Guntert P, Mumenthaler C, Wuthrich K . Torsion angle dynamics for NMR structure calculation with the new program DYANA. J Mol Biol. 1997; 273(1):283-98. DOI: 10.1006/jmbi.1997.1284. View

10.

Conrad N, Wilson S, Steinmetz E, Patturajan M, Brow D, Swanson M . A yeast heterogeneous nuclear ribonucleoprotein complex associated with RNA polymerase II. Genetics. 2000; 154(2):557-71. PMC: 1460961. DOI: 10.1093/genetics/154.2.557. View

11.

Delaglio F, Grzesiek S, Vuister G, Zhu G, Pfeifer J, Bax A . NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J Biomol NMR. 1995; 6(3):277-93. DOI: 10.1007/BF00197809. View

12.

Loya T, ORourke T, Reines D . Yeast Nab3 protein contains a self-assembly domain found in human heterogeneous nuclear ribonucleoprotein-C (hnRNP-C) that is necessary for transcription termination. J Biol Chem. 2012; 288(4):2111-7. PMC: 3554884. DOI: 10.1074/jbc.M112.430678. View

13.

Allepuz-Fuster P, Martinez-Fernandez V, Garrido-Godino A, Alonso-Aguado S, Hanes S, Navarro F . Rpb4/7 facilitates RNA polymerase II CTD dephosphorylation. Nucleic Acids Res. 2014; 42(22):13674-88. PMC: 4267648. DOI: 10.1093/nar/gku1227. View

14.

Varani G . Recent advances in RNA-protein recognition. Curr Opin Struct Biol. 2001; 11(1):53-8. DOI: 10.1016/s0959-440x(00)00164-0. View

15.

Jacks A, Babon J, Kelly G, Manolaridis I, Cary P, Curry S . Structure of the C-terminal domain of human La protein reveals a novel RNA recognition motif coupled to a helical nuclear retention element. Structure. 2003; 11(7):833-43. DOI: 10.1016/s0969-2126(03)00121-7. View

16.

Messias A, Sattler M . Structural basis of single-stranded RNA recognition. Acc Chem Res. 2004; 37(5):279-87. DOI: 10.1021/ar030034m. View

17.

Hobor F, Pergoli R, Kubicek K, Hrossova D, Bacikova V, Zimmermann M . Recognition of transcription termination signal by the nuclear polyadenylated RNA-binding (NAB) 3 protein. J Biol Chem. 2010; 286(5):3645-57. PMC: 3030368. DOI: 10.1074/jbc.M110.158774. View

18.

Mitsuzawa H, Kanda E, Ishihama A . Rpb7 subunit of RNA polymerase II interacts with an RNA-binding protein involved in processing of transcripts. Nucleic Acids Res. 2003; 31(16):4696-701. PMC: 169969. DOI: 10.1093/nar/gkg688. View

19.

Porrua O, Boudvillain M, Libri D . Transcription Termination: Variations on Common Themes. Trends Genet. 2016; 32(8):508-522. DOI: 10.1016/j.tig.2016.05.007. View

20.

Bacikova V, Pasulka J, Kubicek K, Stefl R . Structure and semi-sequence-specific RNA binding of Nrd1. Nucleic Acids Res. 2014; 42(12):8024-38. PMC: 4081072. DOI: 10.1093/nar/gku446. View