Tom Blumenthal

Professor

Photo of Tom Blumenthal

Tom.Blumenthal@Colorado.EDU
Phone: (303) 492-7533
EXT: 2-7533 LAB: 2-0599 FAX: 2-1004

Websites

Lab

Office Location

PORT B331A

Education

Ph.D., John Hopkins University, 1970

Biography

Research Interests:
Mechanisms of pre-mRNA processing: splicing and 3' end formation; logic of gene organization on C. elegans chromosomes: eukaryotic operons

Research Profile:
My laboratory works on the small nematode worm, C. elegans, as a model to understand gene regulation and expression in higher animals. In the process of studying mechanisms of mRNA splicing in C. elegans, our laboratory has discovered that a significant proportion of genes in this animal are arranged and transcribed in a manner quite similar to bacterial operons. This is very unusual in eukaryotes and previously unheard of in animals. The polycistronic pre-mRNAs are converted into monocistronic units by cleavage and polyadenylation and by trans-splicing. We are interested in three general questions. 1) What mechanisms are involved in processing of the polycistronic mRNAs? 2) Do the C. elegans operons serve the purpose of co-regulating genes whose products function together, as operons do in bacteria? and 3) How and when did operons arise during eukaryotic evolution? Like genes in other animals, C. elegans genes contain introns that are spliced out by spliceosomes. However, C. elegans has another type of splicing, mechanistically quite similar to removal of introns, called trans-splicing, in which a short leader is spliced onto the 5' ends of mRNAs. Recognition of a trans-splice site requires only that the pre-mRNA have a 3' splice site with no upstream 5' splice site. Although, C. elegans has two spliced leaders, SL1 and SL2, only SL1 is utilized in such situations. SL2 is reserved for genes located in downstream positions in operons. There is a close connection between formation of the 3' end of the upstream gene and trans-splicing about 100 nucleotides downstream at the 5' end of the next gene in the polycistronic pre-mRNA. Current efforts are directed towards understanding the nature of this connection. We are also studying splice-site recognition in C. elegans, since it appears to be somewhat different from other animals, perhaps because the splicing machinery must cope with both cis-splicing and two kinds of trans-splicing (SL1 and SL2). We have cloned the genes that encode the two subunits of the splicing factor U2AF, which is involved in splice acceptor site recognition. We have discovered that both U2AF subunits interact with the 3' splice site consensus sequence, with the small subunit responsible for recognition of the invariant AG/R at the splice junction. The pre-mRNA that encodes the large subunit of U2AF is alternatively spliced, which may represent a mechanism for autogenous regulation of U2AF levels.

Selected Publications

A global analysis of C. elegans trans-splicing
Allen, MA, Hillier, LW, Waterston, RH, and Blumenthal, T Genome Research, 21(2):255–264. 2011

Identification of transcription start sites of trans-spliced genes: uncovering unusual operon arrangements
Morton, JJ and Blumenthal, T RNA (New York, N.Y.), 17(2):327–337. 2011

Polycistronic pre-mRNA processing in vitro: snRNP and pre-mRNA role reversal in trans-splicing
Lasda, EL, Allen, MA, and Blumenthal, T Genes & Development, 24(15):1645–1658. 2010

RNA polymerase II C-terminal domain phosphorylation patterns in Caenorhabditis elegans operons, polycistronic gene clusters with only one promoter
Garrido-Lecca, A and Blumenthal, T Molecular and Cellular Biology, 30(15):3887–3893. 2010

RNA processing in C. elegans
Morton, JJ and Blumenthal, T Methods in Cell Biology, 106:187–217. 2011

SL trans-splicing in a Caenorhabditis elegans in vitro extract
Lasda, EL, Kuersten, S, and Blumenthal, T Cold Spring Harbor Protocols, 2011(1):pdb.prot5574. 2011

Split genes: another surprise from Giardia
Blumenthal, T Current Biology: CB, 21(4):R162–163. 2011

Trans-splicing
Lasda, EL and Blumenthal, T Wiley Interdisciplinary Reviews. RNA, 2(3):417–434. 2011