eIF2A, an initiator tRNA carrier refractory to eIF2α kinases, functions synergistically with eIF5B

Cellular and Molecular Life Sciences : CMLS
Eunah KimSung Key Jang

Abstract

The initiator tRNA (Met-tRNA iMet ) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNA iMet on the small ribosomal subunit. Eukarya contain the Met-tRNA iMet carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress conditions by the phosphorylation of its α-subunit by stress-activated eIF2α kinases. The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNA iMet on the 40S ribosomal subunit associated with a stress-resistant mRNA under stress conditions. Here, we report that eIF2A interacts and functionally cooperates with eIF5B (a homolog of IF2), and we describe the functional domains of eIF2A that are required for its binding of Met-tRNA iMet , eIF5B, and a stress-resistant mRNA. The results indicate that the eukaryotic eIF5B-eIF2A complex functionally mimics the bacterial IF2 containing ribosome-, GTP-, and initiator tRNA-binding domains in a single polypeptide.

References

Jun 26, 1990·Biochemistry·C O Gualerzi, C L Pon
May 9, 1998·Proceedings of the National Academy of Sciences of the United States of America·N C Kyrpides, C R Woese
Feb 5, 2000·Nature·T V PestovaC U Hellen
Jul 23, 2002·The Journal of Biological Chemistry·Wendy L ZollWilliam C Merrick
Aug 15, 2002·Current Biology : CB·Jing DengNahum Sonenberg
Sep 7, 2002·Molecular and Cellular Biology·Peichuan ZhangDouglas R Cavener
Feb 19, 2005·The Journal of Biological Chemistry·Anton A KomarWilliam C Merrick
Aug 29, 2006·Genesis : the Journal of Genetics and Development·Xiang YuEleanor M Maine
Mar 14, 2008·The EMBO Journal·Tatyana V PestovaChristopher U T Hellen
Jul 8, 2008·Nature Structural & Molecular Biology·Ilya M TereninIvan N Shatsky
Sep 2, 2008·Nature·Angelita SimonettiBruno P Klaholz
Jul 7, 2009·Research in Microbiology·Dario Benelli, Paola Londei
Jul 15, 2009·Molecular Cell·R Andrew MarshallJoseph D Puglisi
Jan 23, 2010·Nature Reviews. Molecular Cell Biology·Richard J JacksonTatyana V Pestova
Jun 23, 2010·The Journal of Biological Chemistry·Sergey E DmitrievIvan N Shatsky
Aug 18, 2010·Genes & Development·Maxim A SkabkinTatyana V Pestova
May 11, 2011·The EMBO Journal·Joon Hyun KimSung Key Jang
Nov 30, 2012·Nucleic Acids Research·Marie NaveauEmmanuelle Schmitt
Sep 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Angelita SimonettiBruno P Klaholz
Nov 10, 2013·Science·Israel S FernándezSjors H W Scheres
Feb 7, 2014·Annual Review of Biochemistry·Alan G Hinnebusch
Feb 27, 2014·Journal of Structural and Functional Genomics·Kazuhiro KashiwagiShigeyuki Yokoyama
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Jul 30, 2014·Nature Structural & Molecular Biology·Hiroshi YamamotoChristian M T Spahn
Sep 28, 2014·Nucleic Acids Research·Vera P Pisareva, Andrey V Pisarev
May 8, 2015·Nature Protocols·Lawrence A KelleyMichael J E Sternberg

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Citations

Feb 24, 2019·International Journal of Molecular Sciences·Emmanuelle SchmittYves Mechulam
Jan 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Bridget Y Huang, Israel S Fernández
Oct 23, 2019·Cold Spring Harbor Perspectives in Medicine·Glenn R Masson, Roger L Williams
Apr 2, 2020·International Journal of Molecular Sciences·Michael Niepmann, Gesche K Gerresheim
Jan 31, 2020·G3 : Genes - Genomes - Genetics·Johnny Cruz-CorchadoVeena Prahlad
Mar 21, 2020·International Journal of Molecular Sciences·Anton A Komar, William C Merrick
Jun 22, 2019·Current Protein & Peptide Science·Zhi ZhengBingdong Sha
Nov 2, 2019·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Joseph A RossNehal Thakor
Nov 19, 2020·Pharmacological Reviews·Muhammad Saad YousufTheodore J Price
Apr 30, 2021·Molecular Genetics and Genomics : MGG·Lei ChenYu-Dong Cai
Jul 20, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·David D Lowe, Denise J Montell
Aug 10, 2021·World Journal of Gastroenterology : WJG·Hui-Chun LiShih-Yen Lo
Sep 14, 2021·Frontiers in Genetics·Prakash Amruth Raj ChukkaNehal Thakor

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Methods Mentioned

BETA
GTPase
nucleotide exchange
pull-down
pull down
in vitro transcription
electrophoresis
co-immunoprecipitation
Co-IP

Software Mentioned

PyMOL
Phyre2

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