Human CLP1 Mutations Alter tRNA Biogenesis, Affecting Both Peripheral and Central Nervous System Function
Standard
Human CLP1 Mutations Alter tRNA Biogenesis, Affecting Both Peripheral and Central Nervous System Function. / Karaca, Ender; Weitzer, Stefan; Pehlivan, Davut; Shiraishi, Hiroshi; Gogakos, Tasos; Hanada, Toshikatsu; Jhangiani, Shalini N; Wiszniewski, Wojciech; Withers, Marjorie; Campbell, Ian M; Erdin, Serkan; Isikay, Sedat; Franco, Luis M; Gonzaga-Jauregui, Claudia; Gambin, Tomasz; Gelowani, Violet; Hunter, Jill V; Yesil, Gozde; Koparir, Erkan; Yilmaz, Sarenur; Brown, Miguel; Briskin, Daniel; Hafner, Markus; Morozov, Pavel; Farazi, Thalia A; Bernreuther, Christian; Glatzel, Markus; Trattnig, Siegfried; Friske, Joachim; Kronnerwetter, Claudia; Bainbridge, Matthew N; Gezdirici, Alper; Seven, Mehmet; Muzny, Donna M; Boerwinkle, Eric; Ozen, Mustafa; Clausen, Tim; Tuschl, Thomas; Yuksel, Adnan; Hess, Andreas; Gibbs, Richard A; Martinez, Javier; Penninger, Josef M; Lupski, James R; Baylor Hopkins Center for Mendelian Genomics.
in: CELL, Jahrgang 157, Nr. 3, 24.04.2014, S. 636-650.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Human CLP1 Mutations Alter tRNA Biogenesis, Affecting Both Peripheral and Central Nervous System Function
AU - Karaca, Ender
AU - Weitzer, Stefan
AU - Pehlivan, Davut
AU - Shiraishi, Hiroshi
AU - Gogakos, Tasos
AU - Hanada, Toshikatsu
AU - Jhangiani, Shalini N
AU - Wiszniewski, Wojciech
AU - Withers, Marjorie
AU - Campbell, Ian M
AU - Erdin, Serkan
AU - Isikay, Sedat
AU - Franco, Luis M
AU - Gonzaga-Jauregui, Claudia
AU - Gambin, Tomasz
AU - Gelowani, Violet
AU - Hunter, Jill V
AU - Yesil, Gozde
AU - Koparir, Erkan
AU - Yilmaz, Sarenur
AU - Brown, Miguel
AU - Briskin, Daniel
AU - Hafner, Markus
AU - Morozov, Pavel
AU - Farazi, Thalia A
AU - Bernreuther, Christian
AU - Glatzel, Markus
AU - Trattnig, Siegfried
AU - Friske, Joachim
AU - Kronnerwetter, Claudia
AU - Bainbridge, Matthew N
AU - Gezdirici, Alper
AU - Seven, Mehmet
AU - Muzny, Donna M
AU - Boerwinkle, Eric
AU - Ozen, Mustafa
AU - Clausen, Tim
AU - Tuschl, Thomas
AU - Yuksel, Adnan
AU - Hess, Andreas
AU - Gibbs, Richard A
AU - Martinez, Javier
AU - Penninger, Josef M
AU - Lupski, James R
AU - Baylor Hopkins Center for Mendelian Genomics
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/4/24
Y1 - 2014/4/24
N2 - CLP1 is a RNA kinase involved in tRNA splicing. Recently, CLP1 kinase-dead mice were shown to display a neuromuscular disorder with loss of motor neurons and muscle paralysis. Human genome analyses now identified a CLP1 homozygous missense mutation (p.R140H) in five unrelated families, leading to a loss of CLP1 interaction with the tRNA splicing endonuclease (TSEN) complex, largely reduced pre-tRNA cleavage activity, and accumulation of linear tRNA introns. The affected individuals develop severe motor-sensory defects, cortical dysgenesis, and microcephaly. Mice carrying kinase-dead CLP1 also displayed microcephaly and reduced cortical brain volume due to the enhanced cell death of neuronal progenitors that is associated with reduced numbers of cortical neurons. Our data elucidate a neurological syndrome defined by CLP1 mutations that impair tRNA splicing. Reduction of a founder mutation to homozygosity illustrates the importance of rare variations in disease and supports the clan genomics hypothesis.
AB - CLP1 is a RNA kinase involved in tRNA splicing. Recently, CLP1 kinase-dead mice were shown to display a neuromuscular disorder with loss of motor neurons and muscle paralysis. Human genome analyses now identified a CLP1 homozygous missense mutation (p.R140H) in five unrelated families, leading to a loss of CLP1 interaction with the tRNA splicing endonuclease (TSEN) complex, largely reduced pre-tRNA cleavage activity, and accumulation of linear tRNA introns. The affected individuals develop severe motor-sensory defects, cortical dysgenesis, and microcephaly. Mice carrying kinase-dead CLP1 also displayed microcephaly and reduced cortical brain volume due to the enhanced cell death of neuronal progenitors that is associated with reduced numbers of cortical neurons. Our data elucidate a neurological syndrome defined by CLP1 mutations that impair tRNA splicing. Reduction of a founder mutation to homozygosity illustrates the importance of rare variations in disease and supports the clan genomics hypothesis.
KW - Abnormalities, Multiple
KW - Animals
KW - Central Nervous System Diseases
KW - Cerebrum
KW - Child, Preschool
KW - Endoribonucleases
KW - Female
KW - Fibroblasts
KW - Humans
KW - Infant
KW - Male
KW - Mice
KW - Mice, Inbred CBA
KW - Microcephaly
KW - Mutation, Missense
KW - Nuclear Proteins
KW - Peripheral Nervous System Diseases
KW - Phosphotransferases
KW - RNA, Transfer
KW - Transcription Factors
U2 - 10.1016/j.cell.2014.02.058
DO - 10.1016/j.cell.2014.02.058
M3 - SCORING: Journal article
C2 - 24766809
VL - 157
SP - 636
EP - 650
JO - CELL
JF - CELL
SN - 0092-8674
IS - 3
ER -