PubMed Health⌕ Search

Biomedical subjects

William O'Gorman

Publications and source records attributed to William O'Gorman.

5 recordsLinked to original sources
PubMed2006

What is so special about oskar wild?

The amazing world of regulatory noncoding RNA has been at the center of biologists' attention in many different fields, from structural biology to transcriptional regulation and cell signaling. The latest example comes from developmental biology. A mutation in the Drosophila gene Oskar reveals a novel developmental function for the 3' untranslated region (UTR) of the oscar mRNA. This study further suggests that, when transcribed, the noncoding parts of the genome may well carry essential regulatory functions fundamental for the coordinated gene expression and development of multicellular organisms.

3' Untranslated Regions↗
PubMed2006

Non-coding RNA in transcription initiation.

Diverse classes of non-coding RNAs, including snRNAs (small nuclear RNAs), play fundamental regulatory roles in gene expression. For example, 7SK RNA and the components of the splicing apparatus U1-U6 snRNAs are implicated in the regulation of transcriptional elongation. The first evidence for the involvement of RNA in the regulation of transcriptional initiation is now emerging. TFIIH (transcription factor IIH), a general transcription initiation factor, appears to associate specifically with U1 snRNA, a core splicing component. Reconstituted transcription in vitro demonstrates an increase in the rate of formation of the first phosphodiester bond by RNA polymerase II in presence of U1 snRNA. Reconstituted re-initiation is also stimulated by U1 snRNA. These results suggest that U1 snRNA functions in the regulation of transcription by RNA polymerase II in addition to its role in RNA processing. The implications of these data extend to the development of new technologies that will allow the identification and analysis of diverse RNA species present as regulatory components in transcription-related ribonucleoprotein complexes.

Models, Biological↗
PubMed2005

Analysis of U1 small nuclear RNA interaction with cyclin H.

TFIIH is a general transcription and repair factor implicated in RNA polymerase II transcription, nucleotide excision repair, and transcription-coupled repair. Genetic defects in TFIIH lead to three distinct inheritable diseases: xeroderma pigmentosa, Cockayne syndrome, and trichothiodystrophy, with xeroderma pigmentosa patients being highly susceptible to skin cancer. Earlier data revealed that the cyclin H subunit of TFIIH associates with U1 small nuclear RNA, a core-splicing component. In addition to its role in RNA processing U1 small nuclear RNA also regulates diverse stages of transcription by RNA polymerase II both in vivo and in vitro, including abortive initiation and re-initiation. Here we identify structural components of U1 and cyclin H implicated in the direct interaction and show how they affect function. Because of unique features of cyclin H we have developed a new methodology for mapping RNA interaction with the full-length cyclin H polypeptide based on electrospray ionization tandem mass spectrometry. We also demonstrate the importance of U1 stem-loops 1 and 2 for the interaction with cyclin H. Functional assays implicate the identified interaction with U1 in regulation of the activity of the cyclin H associated kinase CDK7.

Cross-Linking Reagents↗
PubMed2002

U1 snRNA associates with TFIIH and regulates transcriptional initiation.

Diverse classes of noncoding RNA, including small nuclear RNAs (snRNAs), play fundamental regulatory roles at many stages of gene expression. For example, recent studies have implicated 7SK RNA and components of the splicing apparatus in the regulation of transcriptional elongation. Here we present the first evidence of the involvement of an snRNA in the regulation of transcriptional initiation. We demonstrate that TFIIH, a general transcription initiation factor, specifically associates with U1 snRNA, a core-splicing component. Analysis of the TFIIH-dependent stages of transcription in a reconstituted system demonstrates that U1 stimulates the rate of formation of the first phosphodiester bond by RNA polymerase II. In addition, a promoter-proximal 5' splice site recognized by U1 snRNA stimulates TFIIH-dependent reinitiation of productive transcription. Our results suggest that U1 snRNA functions in regulating transcription by RNA Polymerase II in addition to its role in RNA processing.

Gene Expression Regulation↗