Research ExplorerPublicationseIF2γ mutation that disrupts eIF2 complex integrity links in...

eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.

Standard

eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation. / Borck, Guntram; Shin, Byung-Sik; Stiller, Barbara; Mimouni-Bloch, Aviva; Thiele, Holger; Kim, Joo-Ran; Thakur, Meghna; Skinner, Cindy; Aschenbach, Lara; Smirin-Yosef, Pola; Har-Zahav, Adi; Nürnberg, Gudrun; Altmüller, Janine; Frommolt, Peter; Hofmann, Kay; Konen, Osnat; Nürnberg, Peter; Munnich, Arnold; Schwartz, Charles E; Gothelf, Doron; Colleaux, Laurence; Dever, Thomas E; Kubisch, Christian; Basel-Vanagaite, Lina.

In: MOL CELL, Vol. 48, No. 4, 4, 2012, p. 641-646.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Borck, G, Shin, B-S, Stiller, B, Mimouni-Bloch, A, Thiele, H, Kim, J-R, Thakur, M, Skinner, C, Aschenbach, L, Smirin-Yosef, P, Har-Zahav, A, Nürnberg, G, Altmüller, J, Frommolt, P, Hofmann, K, Konen, O, Nürnberg, P, Munnich, A, Schwartz, CE, Gothelf, D, Colleaux, L, Dever, TE, Kubisch, C & Basel-Vanagaite, L 2012, 'eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.', MOL CELL, vol. 48, no. 4, 4, pp. 641-646. <http://www.ncbi.nlm.nih.gov/pubmed/23063529?dopt=Citation>

APA

Borck, G., Shin, B-S., Stiller, B., Mimouni-Bloch, A., Thiele, H., Kim, J-R., Thakur, M., Skinner, C., Aschenbach, L., Smirin-Yosef, P., Har-Zahav, A., Nürnberg, G., Altmüller, J., Frommolt, P., Hofmann, K., Konen, O., Nürnberg, P., Munnich, A., Schwartz, C. E., ... Basel-Vanagaite, L. (2012). eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation. MOL CELL, 48(4), 641-646. [4]. http://www.ncbi.nlm.nih.gov/pubmed/23063529?dopt=Citation

Vancouver

Borck G, Shin B-S, Stiller B, Mimouni-Bloch A, Thiele H, Kim J-R et al. eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation. MOL CELL. 2012;48(4):641-646. 4.

Bibtex

@article{7c5b0fadd9f7403f8eb916c0c494a971,
title = "eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.",
abstract = "Together with GTP and initiator methionyl-tRNA, translation initiation factor eIF2 forms a ternary complex that binds the 40S ribosome and then scans an mRNA to select the AUG start codon for protein synthesis. Here, we show that a human X-chromosomal neurological disorder characterized by intellectual disability and microcephaly is caused by a missense mutation in eIF2? (encoded by EIF2S3), the core subunit of the heterotrimeric eIF2 complex. Biochemical studies of human cells overexpressing the eIF2? mutant and of yeast eIF2? with the analogous mutation revealed a defect in binding the eIF2? subunit to eIF2?. Consistent with this loss of eIF2 integrity, the yeast eIF2? mutation impaired translation start codon selection and eIF2 function in vivo in a manner that was suppressed by overexpressing eIF2?. These findings directly link intellectual disability to impaired translation initiation, and provide a mechanistic basis for the human disease due to partial loss of eIF2 function.",
keywords = "Humans, Amino Acid Sequence, Base Sequence, Models, Molecular, Mutation, Missense, Intellectual Disability/*genetics, Eukaryotic Initiation Factor-2/chemistry/*genetics/*metabolism, Peptide Chain Initiation, Translational/*genetics, Saccharomyces cerevisiae/*genetics, Saccharomyces cerevisiae Proteins/chemistry/*genetics/*metabolism, Humans, Amino Acid Sequence, Base Sequence, Models, Molecular, Mutation, Missense, Intellectual Disability/*genetics, Eukaryotic Initiation Factor-2/chemistry/*genetics/*metabolism, Peptide Chain Initiation, Translational/*genetics, Saccharomyces cerevisiae/*genetics, Saccharomyces cerevisiae Proteins/chemistry/*genetics/*metabolism",
author = "Guntram Borck and Byung-Sik Shin and Barbara Stiller and Aviva Mimouni-Bloch and Holger Thiele and Joo-Ran Kim and Meghna Thakur and Cindy Skinner and Lara Aschenbach and Pola Smirin-Yosef and Adi Har-Zahav and Gudrun N{\"u}rnberg and Janine Altm{\"u}ller and Peter Frommolt and Kay Hofmann and Osnat Konen and Peter N{\"u}rnberg and Arnold Munnich and Schwartz, {Charles E} and Doron Gothelf and Laurence Colleaux and Dever, {Thomas E} and Christian Kubisch and Lina Basel-Vanagaite",
year = "2012",
language = "English",
volume = "48",
pages = "641--646",
journal = "MOL CELL",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",

}

RIS

TY - JOUR

T1 - eIF2γ mutation that disrupts eIF2 complex integrity links intellectual disability to impaired translation initiation.

AU - Borck, Guntram

AU - Shin, Byung-Sik

AU - Stiller, Barbara

AU - Mimouni-Bloch, Aviva

AU - Thiele, Holger

AU - Kim, Joo-Ran

AU - Thakur, Meghna

AU - Skinner, Cindy

AU - Aschenbach, Lara

AU - Smirin-Yosef, Pola

AU - Har-Zahav, Adi

AU - Nürnberg, Gudrun

AU - Altmüller, Janine

AU - Frommolt, Peter

AU - Hofmann, Kay

AU - Konen, Osnat

AU - Nürnberg, Peter

AU - Munnich, Arnold

AU - Schwartz, Charles E

AU - Gothelf, Doron

AU - Colleaux, Laurence

AU - Dever, Thomas E

AU - Kubisch, Christian

AU - Basel-Vanagaite, Lina

PY - 2012

Y1 - 2012

N2 - Together with GTP and initiator methionyl-tRNA, translation initiation factor eIF2 forms a ternary complex that binds the 40S ribosome and then scans an mRNA to select the AUG start codon for protein synthesis. Here, we show that a human X-chromosomal neurological disorder characterized by intellectual disability and microcephaly is caused by a missense mutation in eIF2? (encoded by EIF2S3), the core subunit of the heterotrimeric eIF2 complex. Biochemical studies of human cells overexpressing the eIF2? mutant and of yeast eIF2? with the analogous mutation revealed a defect in binding the eIF2? subunit to eIF2?. Consistent with this loss of eIF2 integrity, the yeast eIF2? mutation impaired translation start codon selection and eIF2 function in vivo in a manner that was suppressed by overexpressing eIF2?. These findings directly link intellectual disability to impaired translation initiation, and provide a mechanistic basis for the human disease due to partial loss of eIF2 function.

AB - Together with GTP and initiator methionyl-tRNA, translation initiation factor eIF2 forms a ternary complex that binds the 40S ribosome and then scans an mRNA to select the AUG start codon for protein synthesis. Here, we show that a human X-chromosomal neurological disorder characterized by intellectual disability and microcephaly is caused by a missense mutation in eIF2? (encoded by EIF2S3), the core subunit of the heterotrimeric eIF2 complex. Biochemical studies of human cells overexpressing the eIF2? mutant and of yeast eIF2? with the analogous mutation revealed a defect in binding the eIF2? subunit to eIF2?. Consistent with this loss of eIF2 integrity, the yeast eIF2? mutation impaired translation start codon selection and eIF2 function in vivo in a manner that was suppressed by overexpressing eIF2?. These findings directly link intellectual disability to impaired translation initiation, and provide a mechanistic basis for the human disease due to partial loss of eIF2 function.

KW - Humans

KW - Amino Acid Sequence

KW - Base Sequence

KW - Models, Molecular

KW - Mutation, Missense

KW - Intellectual Disability/genetics

KW - Eukaryotic Initiation Factor-2/chemistry/genetics/metabolism

KW - Peptide Chain Initiation, Translational/genetics

KW - Saccharomyces cerevisiae/genetics

KW - Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism

KW - Humans

KW - Amino Acid Sequence

KW - Base Sequence

KW - Models, Molecular

KW - Mutation, Missense

KW - Intellectual Disability/genetics

KW - Eukaryotic Initiation Factor-2/chemistry/genetics/metabolism

KW - Peptide Chain Initiation, Translational/genetics

KW - Saccharomyces cerevisiae/genetics

KW - Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism

M3 - SCORING: Journal article

VL - 48

SP - 641

EP - 646

JO - MOL CELL

JF - MOL CELL

SN - 1097-2765

IS - 4

M1 - 4

ER -