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J R Sanford

Publications and source records attributed to J R Sanford.

9 recordsLinked to original sources
PubMed2005

Multiple roles of arginine/serine-rich splicing factors in RNA processing.

SR proteins (serine- and arginine-rich proteins) are an evolutionarily conserved family consisting of essential pre-mRNA splicing factors. Since their discovery and initial characterization, roles of SR proteins in pre-mRNA splicing and in subsequent steps of post-transcriptional gene expression have expanded significantly. The current hypotheses suggest that SR proteins are multifunctional adaptor molecules that may couple distinct steps of RNA metabolism. In the present study, we will provide an overview of the roles of SR proteins in different steps of post-transcriptional gene expression.

Arginine↗
PubMed2001

Regulation of SR protein localization during development.

Ser-Arg-rich (SR) proteins play numerous roles in spliceosome assembly and the regulation of splice-site selection. Whereas considerable attention has focused on the mechanistic details of SR protein activities, little is known concerning how these splicing regulators are controlled by the cell. Here we examined the subcellular localization of precursor mRNA splicing factors during early development of the nematode Ascaris lumbricoides. In the early embryo, before major zygotic gene activation, most SR proteins, along with RNA polymerase II, are localized in the cytoplasm. As development proceeds, we observe a significant decrease in the cytoplasmic levels of these factors and a concomitant increase in nuclear localization. In contrast, trimethylguanosine-capped small nuclear ribonucleoproteins are predominantly localized in the nucleus throughout this period. We previously showed that the phosphorylation state and activity of SR proteins are regulated during A. lumbricoides embryogenesis. These changes correlate with the onset of precursor mRNA splicing and zygotic transcription. Thus, a coordinate change in the subcellular localization of SR proteins and RNA polymerase II occurs at the transition from reliance on maternally deposited factors to embryonic expression. We propose that before zygotic gene activation, SR proteins and RNA polymerase II are stockpiled in the cytoplasm of early embryos, awaiting signals that lead to their activation.

Active Transport, Cell Nucleus↗
PubMed1999

Developmental regulation of SR protein phosphorylation and activity.

Serine/arginine-rich splicing factors (SR proteins) are substrates for serine phosphorylation that can regulate SR protein function. We have observed gross changes in SR protein phosphorylation during early development coincident with major zygotic gene activation in the nematode Ascaris lumbricoides. These differences correlate with large-scale changes in SR protein activity in promoting both trans- and cis-splicing. Importantly, inactive early stage extracts can be made splicing competent on addition of later stage SR proteins. These data suggest that changes in SR protein phosphorylation have a role in the activation of pre-mRNA splicing during early development.

Animals↗
PubMed1999

SR proteins are required for nematode trans-splicing in vitro.

SR (ser/arg) proteins have been shown to play roles in numerous aspects of pre-mRNA splicing, including modulation of alternative splicing, commitment of substrates to the splicing pathway, and splice site communication. The last of these, splice site communication, is particularly relevant to trans-splicing in which the 5' and 3' exons originate on separate molecules. The participation of SR proteins in naturally occurring, spliced leader RNA-dependent transsplicing has not been examined. Here, we have isolated SR proteins from an organism that performs both trans- and cis-splicing, the nematode Ascaris lumbricoides. To examine their activity in in vitro splicing reactions, we have also developed and characterized an SR protein-depleted whole-cell extract. When tested in this extract, the nematode SR proteins are required for both trans- and cis-splicing. In addition, the state of phosphorylation of the nematode SR proteins is critical to their activity in vitro. Interestingly, mammalian (HeLa) and A. lumbricoides SR proteins exhibit equivalent activities in cis-splicing, while the nematode SR proteins are much more active in trans-splicing. Thus, it appears that SR proteins purified from an organism that naturally trans-splices its pre-mRNAs promote this reaction to a greater extent than do their mammalian counterparts.

Animals↗
PubMed1984

A new approach to tuberculosis notification.

A tuberculosis notification system was initiated which used several sources--the doctor, the diagnostic services of bacteriology, histopathology and radiology, and the pharmacy. The results of six months' notifications have shown that the pharmacy was by far the most complete source (74% of all new cases); doctors notified only 21% of all new cases. The combination of both doctors and the pharmacy was the most complete pair, notifying 85% of all new cases. It is suggested that consideration should be given to the use of pharmacies as a source of notification both in other settings and for other diseases.

Bacteriology↗
PubMed1975

Tolerance of debility in elderly dependants by supporters at home: its significance for hospital practice.

Some 12% of all geriatric admissions to University College Hospital and Whittington Hospital are for patients whose relatives or friends can no longer cope with them at home. The person principally involved with home support was interviewed in 50 such cases. The causes of inability to cope were identified on a quantitative and qualitative basis. The supporters were asked to assess which of the problems identified would have to be alleviated to restore a tolerable situation at home; 46 (92%) were able to do so. Identification of the "alleviation factors" forms a therapeutic and prognostic guideline in this type of admission and may have far-reaching social and economic implications.

Aged↗