title: Hairpin structure within the 3'UTR of DNA polymerase beta mRNA acts as a post-transcriptional regulatory element and interacts with Hax-1.
abstract: Aberrant expression of DNA polymerase beta, a key enzyme involved in base excision repair, leads to genetic instability and carcinogenesis. Pol beta expression has been previously shown to be regulated at the level of transcription, but there is also evidence of post-transcriptional regulation, since rat transcripts undergo alternative polyadenylation, and the resulting 3'UTR contain at least one regulatory element. Data presented here indicate that RNA of the short 3'UTR folds to form a strong secondary structure (hairpin). Its regulatory role was established utilizing a luciferase-based reporter system. Further studies led to the identification of a protein factor, which binds to this element-the anti-apoptotic, cytoskeleton-related protein Hax-1. The results of in vitro binding analysis indicate that the formation of the RNA-protein complex is significantly impaired by disruption of the hairpin motif. We demonstrate that Hax-1 binds to Pol beta mRNA exclusively in the form of a dimer. Biochemical analysis revealed the presence of Hax-1 in mitochondria, but also in the nuclear matrix, which, along with its transcript-binding properties, suggests that Hax-1 plays a role in post-transcriptional regulation of expression of Pol beta.
authors: Cancer Center Institute, Roentgena 5, 02-781 Warsaw, Poland.
authors: Elzbieta
authors: E
authors: Sarnowska
authors: Ewa A
authors: EA
authors: Grzybowska
authors: Krzysztof
authors: K
authors: Sobczak
authors: Ryszard
authors: R
authors: Konopinski
authors: Anna
authors: A
authors: Wilczynska
authors: Maria
authors: M
authors: Szwarc
authors: Tomasz J
authors: TJ
authors: Sarnowski
authors: Wlodzimierz J
authors: WJ
authors: Krzyzosiak
authors: Janusz A
authors: JA
authors: Siedlecki
mesh_terms: D020413:3' Untranslated Regions / Q000737:chemistry*; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D045744:Cell Line, Tumor; D019951:DNA Polymerase beta / Q000235:genetics*; D019281:Dimerization; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015530:Nuclear Matrix / Q000737:chemistry; D009690:Nucleic Acid Conformation; D051381:Rats; D038621:Regulatory Sequences, Ribonucleic Acid; D014466:Ultraviolet Rays
chemical_list: D020413:3' Untranslated Regions; D002352:Carrier Proteins; C510653:Hax1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D038621:Regulatory Sequences, Ribonucleic Acid; D019951:DNA Polymerase beta
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