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Joan Steitz, Ph.D.
HHMI, Yale University, New Haven, CT
Presented April
12, 2003 – ASBMB Annual Meeting, San Diego, CA
2003 FASEB Experimental Biology Symposium
"Pre-mRNA Splicing: The Tie That
Binds"
Current excitement in
the field of gene expression derives from the realization that multiple linkages
connect the various steps, which have traditionally been studied in isolation.
In higher eukaryotes, pre-mRNA splicing is a central process essential for
converting information stored in the DNA into protein for the vast majority of
genes.
The history of the
discovery of snRNPs (small nuclear ribonucleoproteins) and their involvement in
splicing will be briefly reviewed. Then, two ongoing examples that link
splicing to other steps in gene expression will be considered.
The first concerns
the biogenesis of snoRNPs (small nucleolar ribonucleoproteins) in vertebrate
cells. SnoRNPs are responsible for the introduction of nucleotide modifications
into ribosomal and spliceosomal RNAs. The snoRNA components of snoRNPs
represent remnants of introns, which are assembled with specific snoRNP proteins
coordinately with removal of their host introns from pre-mRNAs by the
spliceosome. Molecular interactions that underlie this synergy between splicing
and snoRNP biogenesis have been dissected in an in vitro system where
splicing and snoRNA processing/assembly are coupled.
The second involves
the export of newly synthesized mRNAs from the nucleus to the cytoplasm.
Certain members of a class of essential splicing factors known as SR(Ser/Arg)-rich
proteins shuttle between the nucleus and cytoplasm. These proteins bind to
pre-mRNA transcripts to assist spliceosome assembly and then remain bound after
splicing to serve as adaptors for mRNA export through the nuclear pores. Their
mode of interaction with TAP, a receptor responsible for the nucleocytoplasmic
transport of most mRNAs, will be discussed.
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