Premium
RECQ1 interacts with rDNA and promotes pre‐rRNA transcription
Author(s) -
Parvathaneni Swetha,
Lu Xing,
Sharma Sudha
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.906.10
Subject(s) - ribosome biogenesis , biology , transcription (linguistics) , ribosomal rna , rna polymerase i , nucleolus , ribosomal dna , ribosome , rna helicase a , genetics , microbiology and biotechnology , helicase , rna , gene , rna polymerase , linguistics , philosophy , phylogenetics , cytoplasm
Ribosomal DNA (rDNA) is organized in tandem repeats and presents a significant barrier to replication fork progression. RECQ1 helicase is a major player in maintaining replication fork progression under stress. Nascent rRNAs generated during RNA Polymerase (Pol) I‐mediated rDNA transcription have a tendency to re‐associate with template rDNA and form rRNA:rDNA hybrids that can inhibit rRNA transcription, impede replication fork and facilitate rDNA recombination. Here, we show that RECQ1 is enriched in the nucleolus, the factory of ribosome biogenesis. RECQ1‐depletion in HeLa and U2OS cells significantly reduces pre‐rRNA levels. Genetic rescue experiments indicate a helicase activity‐dependent function of RECQ1 in rRNA biogenesis. RECQ1 binds to the rDNA promoter, enhances RNA pol I recruitment to rDNA promoter and enhances rDNA promoter activity. Depletion of RECQ1 causes ribosomal stress, dysregulated mRNA translation and reduced global translation. Consistent with this disruption of ribosome biogenesis, RECQ1‐depleted cells display impaired growth and proliferation. Collectively, these results identify rDNA as a novel target of RECQ1 helicase to maintain rRNA transcription and ribogenesis. Support or Funding Information This work was funded by the NIGMS/NIH grant SC1GM093999 to Sudha Sharma. We also acknowledge support from the NIMHD/NIH award number G12MD007597 and NIA/NIH award number 1R25 AG047843‐02. We thank Drs. Ritu Chaudhary, Xiaoling Li and Ashish Lal (NCI) for their help and support.