Kiyoshi Nagai (June 25, 1949 – September 27, 2019) was a Japanese

structural biologist Structural biology is a field that is many centuries old which, and as defined by the Journal of Structural Biology, deals with structural analysis of living material (formed, composed of, and/or maintained and refined by living cells) at every le ...

at the

MRC Laboratory of Molecular Biology The Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) is a research institute in Cambridge, England, involved in the revolution in molecular biology which occurred in the 1950–60s. Since then it has remained a major medical r ...

Cambridge, UK. He was known for his work on the mechanism of

RNA splicing RNA splicing is a process in molecular biology where a newly-made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). It works by removing all the introns (non-coding regions of RNA) and ''splicing'' b ...

and structures of the

spliceosome A spliceosome is a large ribonucleoprotein (RNP) complex found primarily within the nucleus of eukaryotic cells. The spliceosome is assembled from small nuclear RNAs (snRNA) and numerous proteins. Small nuclear RNA (snRNA) molecules bind to specifi ...

Education

Nagai studied at

Osaka University , abbreviated as , is a public research university located in Osaka Prefecture, Japan. It is one of Japan's former Imperial Universities and a Designated National University listed as a "Top Type" university in the Top Global University Project. ...

and earned a

Doctor of Philosophy A Doctor of Philosophy (PhD, Ph.D., or DPhil; Latin: or ') is the most common Academic degree, degree at the highest academic level awarded following a course of study. PhDs are awarded for programs across the whole breadth of academic fields ...

under the supervision of Hideki Morimoto working on the

allosteric In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric site ...

effect in

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...

Career and research

In 1981 Nagai moved to the

where he worked as a post-doc with

Max Perutz Max Ferdinand Perutz (19 May 1914 – 6 February 2002) was an Austrian-born British molecular biologist, who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of haemoglobin and myoglobin. He went ...

on overproduction of eukaryotic proteins in ''

E. coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

.'' He produced recombinant

and studied its properties and evolution by crystallography and mutagenesis. 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 Darwin College is a constituent college of the University of Cambridge. Founded on 28 July 1964, Darwin was Cambridge University's first graduate-only college, and also the first to admit both men and women. The college is named after one of the ...

in 1993. In 1990 his group solved the first structure of an

RRM RRM may refer to: * River and Rowing Museum in Henley-on-Thames, Oxfordshire, England * Radio resource management * RNA recognition motif * Robotic Refueling Mission, carried by STS-135 to the International Space Station * A Residential Reentry Man ...

(RNA recognition motif) protein, U1A, and in 1994 showed how it specifically binds RNA. Subsequent work involved

crystallographic Crystallography is the experimental science of determining the arrangement of atoms in crystalline solids. Crystallography is a fundamental subject in the fields of materials science and solid-state physics (condensed matter physics). The word ...

studies of other components of the

, a large macromolecular machine that catalyses

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

s, including components of the U2 snRNP and the Sm proteins and culminating in the crystal structures of the full U1 snRNP and the U5 snRNP components

Prp8 Prp8 refers to both the Prp8 protein and Prp8 gene. Prp8's name originates from its involvement in pre-mRNA processing. The Prp8 protein is a large, highly conserved, and unique protein that resides in the catalytic core of the spliceosome and has ...

and Brr2. From 2014, Nagai's group used

cryo-electron microscopy Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample sol ...

to study the spliceosome. Structures of the U5.U4/U6 tri-snRNP gave the first structural insights into the assembly of the spliceosome. Nagai's subsequent structures of spliceosomes in various stages of assembly and catalysis combined with structures from the groups of Reinhard Lührmann,

Yigong Shi Shi Yigong (; born May 1967) is a Chinese biophysicist who serves as founding and the current president of Westlake University since April 2018. He previously served as vice president of Tsinghua University from 2015 to 2018 and dean of Tsing ...

and others have provided crucial insight into the catalytic mechanism of pre-mRNA splicing.

Awards

* 2000 Fellow of the

Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...

* 1999 Member,

European Molecular Biology Organisation The European Molecular Biology Organization (EMBO) is a professional, non-profit organization of more than 1,800 life scientists. Its goal is to promote research in life science and enable international exchange between scientists. It co-funds cour ...

(EMBO) * 2000 Novartis Medal of the Biochemical Society

References

{{DEFAULTSORT:Nagai, Kiyoshi Japanese biologists Structural biologists Fellows of the Royal Society Osaka University alumni Members of the European Molecular Biology Organization Fellows of Darwin College, Cambridge 1949 births 2019 deaths 20th-century Japanese scientists 21st-century Japanese scientists 21st-century biologists 20th-century biologists People from Osaka Japanese expatriates in the United Kingdom