The Conserved AU Dinucleotide at the 5' End of Nascent U1 SnRNA is Optimized for the Interaction with Nuclear Cap-binding-complex

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2017 Sep 22

PMID 28934473

Citations 5

Authors

Chung-Shu Yeh

Shang-Lin Chang

Jui-Hui Chen

Hsuan-Kai Wang

Yue-Chang Chou

Chun-Hsiung Wang

Shih-Hsin Huang

Amy Larson

Jeffrey A Pleiss

Wei-Hau Chang

Tien-Hsien Chang

Affiliations

Soon will be listed here.

Abstract

Splicing is initiated by a productive interaction between the pre-mRNA and the U1 snRNP, in which a short RNA duplex is established between the 5' splice site of a pre-mRNA and the 5' end of the U1 snRNA. A long-standing puzzle has been why the AU dincucleotide at the 5'-end of the U1 snRNA is highly conserved, despite the absence of an apparent role in the formation of the duplex. To explore this conundrum, we varied this AU dinucleotide into all possible permutations and analyzed the resulting molecular consequences. This led to the unexpected findings that the AU dinucleotide dictates the optimal binding of cap-binding complex (CBC) to the 5' end of the nascent U1 snRNA, which ultimately influences the utilization of U1 snRNP in splicing. Our data also provide a structural interpretation as to why the AU dinucleotide is conserved during evolution.

Citing Articles

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References

Mouaikel J, Verheggen C, Bertrand E, Tazi J, Bordonne R . Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs requires a conserved methyltransferase that is localized to the nucleolus. Mol Cell. 2002; 9(4):891-901. DOI: 10.1016/s1097-2765(02)00484-7. View

Inada M, Pleiss J . Genome-wide approaches to monitor pre-mRNA splicing. Methods Enzymol. 2010; 470:51-75. DOI: 10.1016/S0076-6879(10)70003-3. View

Abovich N, Rosbash M . Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 1997; 89(3):403-12. DOI: 10.1016/s0092-8674(00)80221-4. View

Yan C, Wan R, Bai R, Huang G, Shi Y . Structure of a yeast step II catalytically activated spliceosome. Science. 2016; 355(6321):149-155. DOI: 10.1126/science.aak9979. View

Pleiss J, Whitworth G, Bergkessel M, Guthrie C . Rapid, transcript-specific changes in splicing in response to environmental stress. Mol Cell. 2007; 27(6):928-37. PMC: 2081968. DOI: 10.1016/j.molcel.2007.07.018. View

Roca X, Akerman M, Gaus H, Berdeja A, Bennett C, Krainer A . Widespread recognition of 5' splice sites by noncanonical base-pairing to U1 snRNA involving bulged nucleotides. Genes Dev. 2012; 26(10):1098-109. PMC: 3360564. DOI: 10.1101/gad.190173.112. View

Shultzaberger R, Chen Z, Lewis K, Schneider T . Anatomy of Escherichia coli sigma70 promoters. Nucleic Acids Res. 2006; 35(3):771-88. PMC: 1807945. DOI: 10.1093/nar/gkl956. View

Will C, Luhrmann R . Spliceosome structure and function. Cold Spring Harb Perspect Biol. 2011; 3(7). PMC: 3119917. DOI: 10.1101/cshperspect.a003707. View

Roca X, Krainer A, Eperon I . Pick one, but be quick: 5' splice sites and the problems of too many choices. Genes Dev. 2013; 27(2):129-44. PMC: 3566305. DOI: 10.1101/gad.209759.112. View

10.

Arning S, Gruter P, Bilbe G, Kramer A . Mammalian splicing factor SF1 is encoded by variant cDNAs and binds to RNA. RNA. 1996; 2(8):794-810. PMC: 1369416. View

11.

Schwer B, Chang J, Shuman S . Structure-function analysis of the 5' end of yeast U1 snRNA highlights genetic interactions with the Msl5*Mud2 branchpoint-binding complex and other spliceosome assembly factors. Nucleic Acids Res. 2013; 41(15):7485-500. PMC: 3753624. DOI: 10.1093/nar/gkt490. View

12.

Seraphin B, Kretzner L, Rosbash M . A U1 snRNA:pre-mRNA base pairing interaction is required early in yeast spliceosome assembly but does not uniquely define the 5' cleavage site. EMBO J. 1988; 7(8):2533-8. PMC: 457124. DOI: 10.1002/j.1460-2075.1988.tb03101.x. View

13.

Fortes P, Kufel J, Fornerod M, Lafontaine D, Tollervey D, Mattaj I . Genetic and physical interactions involving the yeast nuclear cap-binding complex. Mol Cell Biol. 1999; 19(10):6543-53. PMC: 84624. DOI: 10.1128/MCB.19.10.6543. View

14.

Colot H, Stutz F, Rosbash M . The yeast splicing factor Mud13p is a commitment complex component and corresponds to CBP20, the small subunit of the nuclear cap-binding complex. Genes Dev. 1996; 10(13):1699-708. DOI: 10.1101/gad.10.13.1699. View

15.

Michaud S, REED R . A functional association between the 5' and 3' splice site is established in the earliest prespliceosome complex (E) in mammals. Genes Dev. 1993; 7(6):1008-20. DOI: 10.1101/gad.7.6.1008. View

16.

Gornemann J, Kotovic K, Hujer K, Neugebauer K . Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol Cell. 2005; 19(1):53-63. DOI: 10.1016/j.molcel.2005.05.007. View

17.

Zhuang Y, Weiner A . A compensatory base change in U1 snRNA suppresses a 5' splice site mutation. Cell. 1986; 46(6):827-35. DOI: 10.1016/0092-8674(86)90064-4. View

18.

Morris G, Huey R, Lindstrom W, Sanner M, Belew R, Goodsell D . AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16):2785-91. PMC: 2760638. DOI: 10.1002/jcc.21256. View

19.

Kondo Y, Oubridge C, van Roon A, Nagai K . Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition. Elife. 2015; 4. PMC: 4383343. DOI: 10.7554/eLife.04986. View

20.

Bertram K, Agafonov D, Liu W, Dybkov O, Will C, Hartmuth K . Cryo-EM structure of a human spliceosome activated for step 2 of splicing. Nature. 2017; 542(7641):318-323. DOI: 10.1038/nature21079. View