hnRNP A2, a potential ssDNA/RNA molecular adapter at the telomere.
The heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a multi-tasking protein that acts in the cytoplasm and nucleus. We have explored the possibility that this protein is associated with telomeres and participates in their maintenance. Rat brain hnRNP A2 was shown to have two nucleic acid binding sites. In the presence of heparin one site binds single-stranded oligodeoxyribonucleotides irrespective of sequence but not the corresponding oligoribonucleotides. Both the hnRNP A2-binding cis-acting element for the cytoplasmic RNA trafficking element, A2RE, and the ssDNA telomere repeat match a consensus sequence for binding to a second sequence-specific site identified by mutational analysis. hnRNP A2 protected the telomeric repeat sequence, but not the complementary sequence, against DNase digestion: the glycine-rich domain was found to be necessary, but not sufficient, for protection. The N-terminal RRM (RNA recognition motif) and tandem RRMs of hnRNP A2 also bind the single-stranded, template-containing segment of telomerase RNA. hnRNP A2 colocalizes with telomeric chromatin in the subset of PML bodies that are a hallmark of ALT cells, reinforcing the evidence for hnRNPs having a role in telomere maintenance. Our results support a model in which hnRNP A2 acts as a molecular adapter between single-stranded telomeric repeats, or telomerase RNA, and another segment of ssDNA.
Moran-Jones
Kim
K
Department of Biochemistry and Molecular Biology, The University of Queensland QLD 4072, Australia.
Wayman
Lyndal
L
Kennedy
Derek D
DD
Reddel
Roger R
RR
Sara
Sergio
S
Snee
Mark J
MJ
Smith
Ross
R
D000818:Animals; D001665:Binding Sites; D022003:Cell Nucleus Structures / Q000737:chemistry; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000378:metabolism; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D000071156:Promyelocytic Leukemia Protein; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D019098:Telomerase / Q000737:chemistry / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins
D004277:DNA, Single-Stranded; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D035341:Telomeric Repeat Binding Protein 2; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C439768:hnRNP A2; C422952:telomerase RNA; C070576:PML protein, human; D012313:RNA; D019098:Telomerase; D003851:Deoxyribonucleases