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WDR74 participates in an early cleavage of the pre-rRNA processing pathway in cooperation with the nucleolar AAA-ATPase NVL2
- Source :
- Biochemical and Biophysical Research Communications. 495:116-123
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- WD repeat-containing protein 74 (WDR74), a nucleolar-localized protein, is the mammalian ortholog of Nsa1, a 60S ribosome assembly factor in yeast. We previously showed that WDR74 associates with MTR4, the nuclear exosome-assisting RNA helicase, whose dissociation is prohibited by an ATPase-deficient mutant of the AAA-type chaperone NVL2. However, the functions and regulation of WDR74 during ribosome biogenesis in cooperation with NVL2 remains unknown. Here, we demonstrated that knockdown of WDR74 leads to significant defects in the pre-rRNA cleavage within the internal transcribed spacer 1 (ITS1), occurring in an early stage of the processing pathway. Interestingly, when the dissociation of WDR74 from the MTR4-containing exonuclease complex was impaired upon expression of the mutant NVL2, the same processing defect, with partial migration of WDR74 from the nucleolus towards the nucleoplasm, was observed. In the nucleoplasm, an increased interaction between WDR74 and MTR4 was detected by in situ proximity ligation assay. Therefore, the dissociation of WDR74 from MTR4 in a late stage of rRNA synthesis is thought to be required for appropriate maturation of the pre-60S particles. These results suggest that the spatiotemporal regulation of ribosome biogenesis in the nucleolus is mediated by the ATPase activity of NVL2.
- Subjects :
- 0301 basic medicine
Nucleolus
5.8S ribosomal RNA
Biophysics
Ribosome biogenesis
Biology
Biochemistry
Ribosome assembly
03 medical and health sciences
0302 clinical medicine
RNA Precursors
Humans
RNA Processing, Post-Transcriptional
RRNA processing
Molecular Biology
Nucleoplasm
Exosome Multienzyme Ribonuclease Complex
RNA-Binding Proteins
Cell Biology
RNA Helicase A
AAA proteins
Cell biology
Protein Transport
HEK293 Cells
030104 developmental biology
Gene Knockdown Techniques
030220 oncology & carcinogenesis
ATPases Associated with Diverse Cellular Activities
Mutant Proteins
Carrier Proteins
Ribosomes
Cell Nucleolus
RNA Helicases
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 495
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....f412829d724d7fdb2a942105c572951b