Proteomics

Dataset Information

0

RNA polymerase I transcription disturbances lead to instable ribosomes in Cockayne syndrome


ABSTRACT: DNA-repair factors of the Nucleotide -Excision-Repair (NER) pathway are part of the basal transcription apparatus of RNA polymerase I. Mutations in these factors can give rise to developmental disorders with symptoms that are typical for the aging body. Here we show that in Cockayne syndrome (CS) RNA polymerase I transcription elongation and the processing of the pre-rRNA are disturbed. The mature 18S rRNA is reduced and isolated ribosomes lack specific ribosomal proteins. Ribosomal proteins are susceptible to unfolding and the proteome of CS cells is heat-sensitive, indicating misfolded proteins and an error prone translation process in CS cells. Pharmaceutical chaperones restored impaired cellular proliferation. Thus, we provide evidence for severe malfunction in protein synthesis which together with a loss of proteostasis constitute the underlying pathophysiology in CS.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Cockayne Syndrome

SUBMITTER: Christina Ludwig  

LAB HEAD: Christina Ludwig

PROVIDER: PXD024478 | Pride | 2021-11-16

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
BBM_321_P153_02_FRH_001.raw Raw
BBM_321_P153_02_FRH_002.raw Raw
BBM_321_P153_02_FRH_003.raw Raw
BBM_321_P153_02_FRH_004.raw Raw
BBM_321_P153_02_FRH_005.raw Raw
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Publications

Cockayne Syndrome-Associated CSA and CSB Mutations Impair Ribosome Biogenesis, Ribosomal Protein Stability, and Global Protein Folding.

Qiang Mingyue M   Khalid Fatima F   Phan Tamara T   Ludwig Christina C   Scharffetter-Kochanek Karin K   Iben Sebastian S  

Cells 20210628 7


Cockayne syndrome (CS) is a developmental disorder with symptoms that are typical for the aging body, including subcutaneous fat loss, alopecia, and cataracts. Here, we show that in the cells of CS patients, RNA polymerase I transcription and the processing of the pre-rRNA are disturbed, leading to an accumulation of the 18S-E intermediate. The mature 18S rRNA level is reduced, and isolated ribosomes lack specific ribosomal proteins of the small 40S subunit. Ribosomal proteins are susceptible to  ...[more]

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