Kiyoshi Nagai Explained

Kiyoshi Nagai
Birth Date:25 June 1949
Birth Place:Osaka, Japan
Death Place:Cambridge, United Kingdom
Nationality:Japanese
Workplaces:MRC Laboratory of Molecular Biology
Alma Mater:Osaka University (BSc, MSc, PhD)
Thesis Year:1978
Doctoral Advisor:Hideki Morimoto
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Kiyoshi Nagai (June 25, 1949 – September 27, 2019) was a Japanese structural biologist at the MRC Laboratory of Molecular Biology Cambridge, UK. He was known for his work on the mechanism of RNA splicing and structures of the spliceosome.

Education

Nagai studied at Osaka University and earned a Doctor of Philosophy under the supervision of Hideki Morimoto working on the allosteric effect in hemoglobin.[1]

Career and research

In 1981 Nagai moved to the MRC Laboratory of Molecular Biology where he worked as a post-doc with Max Perutz on overproduction of eukaryotic proteins in E. coli. He produced recombinant hemoglobin and studied its properties and evolution by crystallography and mutagenesis.[2] [3] In 1987 he became a tenured group leader at the LMB and was joint head of the Division of Structural Studies from 2000 to 2010. He was appointed fellow of Darwin College, Cambridge in 1993.[4]

In 1990 his group solved the first structure of an RRM (RNA recognition motif) protein, U1A,[5] and in 1994 showed how it specifically binds RNA.[6] Subsequent work involved crystallographic studies of other components of the spliceosome, a large macromolecular machine that catalyses RNA splicing in eukaryotes, including components of the U2 snRNP[7] and the Sm proteins[8] and culminating in the crystal structures of the full U1 snRNP[9] [10] and the U5 snRNP components Prp8[11] and Brr2.[12]

From 2014, Nagai's group used cryo-electron microscopy to study the spliceosome. Structures of the U5.U4/U6 tri-snRNP gave the first structural insights into the assembly of the spliceosome.[13] [14] Nagai's subsequent structures of spliceosomes in various stages of assembly and catalysis[15] [16] combined with structures from the groups of Reinhard Lührmann, Yigong Shi and others have provided crucial insight into the catalytic mechanism of pre-mRNA splicing.

Awards

Notes and References

  1. Galej. Wojciech P.. Toor. Navtej. Newman. Andrew J.. Nagai. Kiyoshi. 2018-04-25. Molecular Mechanism and Evolution of Nuclear Pre-mRNA and Group II Intron Splicing: Insights from Cryo-Electron Microscopy Structures. Chemical Reviews. 118. 8. 4156–4176. 10.1021/acs.chemrev.7b00499. 1520-6890. 29377672.
  2. Nagai. K.. Thøgersen. H. C.. 1984. Generation of beta-globin by sequence-specific proteolysis of a hybrid protein produced in Escherichia coli. Nature. 309. 5971. 810–812. 0028-0836. 6330564. 10.1038/309810a0. 1984Natur.309..810N. 4307749.
  3. Nagai. K.. Perutz. M. F.. Poyart. C.. 1985. Oxygen binding properties of human mutant hemoglobins synthesized in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America. 82. 21. 7252–7255. 0027-8424. 390827. 3903751. 10.1073/pnas.82.21.7252. 1985PNAS...82.7252N. free .
  4. Web site: Master & fellows www.darwin.cam.ac.uk. www.darwin.cam.ac.uk. 2018-12-09.
  5. Nagai. K.. Oubridge. C.. Jessen. T. H.. Li. J.. Evans. P. R.. 1990-12-06. Crystal structure of the RNA-binding domain of the U1 small nuclear ribonucleoprotein A. Nature. 348. 6301. 515–520. 10.1038/348515a0. 0028-0836. 2147232. 1990Natur.348..515N. 4336326.
  6. Oubridge. C.. Ito. N.. Evans. P. R.. Teo. C. H.. Nagai. K.. 1994-12-01. Crystal structure at 1.92 A resolution of the RNA-binding domain of the U1A spliceosomal protein complexed with an RNA hairpin. Nature. 372. 6505. 432–438. 10.1038/372432a0. 0028-0836. 7984237. 1994Natur.372..432O. 9404488.
  7. Price. S. R.. Evans. P. R.. Nagai. K.. 1998-08-13. Crystal structure of the spliceosomal U2B"-U2A' protein complex bound to a fragment of U2 small nuclear RNA. Nature. 394. 6694. 645–650. 10.1038/29234. 0028-0836. 9716128. 1998Natur.394..645P. 204999419.
  8. Kambach. C.. Walke. S.. Young. R.. Avis. J. M.. de la Fortelle. E.. Raker. V. A.. Lührmann. R.. Li. J.. Nagai. K.. 1999-02-05. Crystal structures of two Sm protein complexes and their implications for the assembly of the spliceosomal snRNPs. Cell. 96. 3. 375–387. 0092-8674. 10025403. 10.1016/S0092-8674(00)80550-4. 17379935. free.
  9. Pomeranz Krummel. Daniel A.. Oubridge. Chris. Leung. Adelaine K. W.. Li. Jade. Nagai. Kiyoshi. 2009-03-26. Crystal structure of human spliceosomal U1 snRNP at 5.5 A resolution. Nature. 458. 7237. 475–480. 10.1038/nature07851. 1476-4687. 2673513. 19325628. 2009Natur.458..475P.
  10. Kondo. Yasushi. Oubridge. Chris. van Roon. Anne-Marie M.. Nagai. Kiyoshi. 2015-01-02. Crystal structure of human U1 snRNP, a small nuclear ribonucleoprotein particle, reveals the mechanism of 5' splice site recognition. eLife. 4. 10.7554/eLife.04986. 2050-084X. 4383343. 25555158 . free .
  11. Galej. Wojciech P.. Oubridge. Chris. Newman. Andrew J.. Nagai. Kiyoshi. 2013-01-31. Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature. 493. 7434. 638–643. 10.1038/nature11843. 1476-4687. 3672837. 23354046. 2013Natur.493..638G.
  12. Nguyen. Thi Hoang Duong. Li. Jade. Galej. Wojciech P.. Oshikane. Hiroyuki. Newman. Andrew J.. Nagai. Kiyoshi. 2013-06-04. Structural basis of Brr2-Prp8 interactions and implications for U5 snRNP biogenesis and the spliceosome active site. Structure. 21. 6. 910–919. 10.1016/j.str.2013.04.017. 1878-4186. 3677097. 23727230.
  13. Nguyen. Thi Hoang Duong. Galej. Wojciech P.. Bai. Xiao-chen. Savva. Christos G.. Newman. Andrew J.. Scheres. Sjors H. W.. Nagai. Kiyoshi. 2015-07-02. The architecture of the spliceosomal U4/U6.U5 tri-snRNP. Nature. 523. 7558. 47–52. 10.1038/nature14548. 1476-4687. 4536768. 26106855. 2015Natur.523...47N.
  14. Nguyen. Thi Hoang Duong. Galej. Wojciech P.. Bai. Xiao-Chen. Oubridge. Chris. Newman. Andrew J.. Scheres. Sjors H. W.. Nagai. Kiyoshi. 2016-02-18. Cryo-EM structure of the yeast U4/U6.U5 tri-snRNP at 3.7 Å resolution. Nature. 530. 7590. 298–302. 10.1038/nature16940. 1476-4687. 4762201. 26829225. 2016Natur.530..298N.
  15. Fica. Sebastian M.. Nagai. Kiyoshi. 2017-10-05. Cryo-electron microscopy snapshots of the spliceosome: structural insights into a dynamic ribonucleoprotein machine. Nature Structural & Molecular Biology. 24. 10. 791–799. 10.1038/nsmb.3463. 1545-9985. 28981077. 6386135.
  16. Scheres. Sjors Hw. Nagai. Kiyoshi. 2017. CryoEM structures of spliceosomal complexes reveal the molecular mechanism of pre-mRNA splicing. Current Opinion in Structural Biology. 46. 130–139. 10.1016/j.sbi.2017.08.001. 1879-033X. 28888105.
  17. Web site: Kiyoshi Nagai Royal Society. royalsociety.org. en-gb. 2018-12-09.
  18. Newman . Andy . Luisi . Ben . 2022 . Kiyoshi Nagai. 25 June 1949—27 September 2019 . Biographical Memoirs of Fellows of the Royal Society . 72. 275–291 . 10.1098/rsbm.2021.0043 . 247453651 . free .
  19. Web site: Find people in the EMBO Communities. people.embo.org. 2018-12-09.
  20. Nagai. K.. Muto. Y.. Pomeranz Krummel. D. A.. Kambach. C.. Ignjatovic. T.. Walke. S.. Kuglstatter. A.. 2001. Structure and assembly of the spliceosomal snRNPs. Novartis Medal Lecture. Biochemical Society Transactions. 29. Pt 2. 15–26. 0300-5127. 11356120. 10.1042/bst0290015.

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