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HnRNP A1 phosphorylated by VRK1 stimulates telomerase and its binding to telomeric DNA sequence.
- Source :
-
Nucleic acids research [Nucleic Acids Res] 2012 Sep 01; Vol. 40 (17), pp. 8499-518. Date of Electronic Publication: 2012 Jun 26. - Publication Year :
- 2012
-
Abstract
- The telomere integrity is maintained via replication machinery, telomere associated proteins and telomerase. Many telomere associated proteins are regulated in a cell cycle-dependent manner. Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a single-stranded oligonucleotide binding protein, is thought to play a pivotal role in telomere maintenance. Here, we identified hnRNP A1 as a novel substrate for vaccinia-related kinase 1 (VRK1), a cell cycle regulating kinase. Phosphorylation by VRK1 potentiates the binding of hnRNP A1 to telomeric ssDNA and telomerase RNA in vitro and enhances its function for telomerase reaction. VRK1 deficiency induces a shortening of telomeres with an abnormal telomere arrangement and activation of DNA-damage signaling in mouse male germ cells. Together, our data suggest that VRK1 is required for telomere maintenance via phosphorylation of hnRNP A1, which regulates proteins associated with the telomere and telomerase RNA.
- Subjects :
- Animals
Base Sequence
Binding Sites
Cell Cycle genetics
DNA, Single-Stranded chemistry
HeLa Cells
Heterogeneous Nuclear Ribonucleoprotein A1
Heterogeneous-Nuclear Ribonucleoprotein Group A-B chemistry
Humans
Male
Mice
Phosphorylation
Protein Serine-Threonine Kinases deficiency
RNA metabolism
Spermatogonia metabolism
Telomere chemistry
DNA, Single-Stranded metabolism
Heterogeneous-Nuclear Ribonucleoprotein Group A-B metabolism
Intracellular Signaling Peptides and Proteins metabolism
Protein Serine-Threonine Kinases metabolism
Telomerase metabolism
Telomere metabolism
Telomere Homeostasis
Subjects
Details
- Language :
- English
- ISSN :
- 1362-4962
- Volume :
- 40
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Nucleic acids research
- Publication Type :
- Academic Journal
- Accession number :
- 22740652
- Full Text :
- https://doi.org/10.1093/nar/gks634