This process describes the conversion of precursor messenger RNA into mature messenger RNA (mRNA). The pre-mRNA molecule undergoes three main modifications. These modifications are 5' capping, 3' polyadenylation, and RNA splicing, which occur in the cell nucleus before the RNA is translated.
5' Capping: Capping of the pre-mRNA involves the addition of 7-methylguanosine (m7G) to the 5' end. The cap protects the 5' end of the primary RNA transcript from attack by ribonucleases that have specificity to the 3'5' phosphodiester bonds.
3' Processing: The pre-mRNA processing at the 3' end of the RNA molecule involves cleavage of its 3' end and then the addition of about 200 adenine residues to form a poly(A) tail. As the poly(A) tails is synthesised, it binds multiple copies of poly(A) binding protein, which protects the 3'end from ribonuclease digestion.
Splicing: RNA splicing is the process by which introns, regions of RNA that do not code for protein, are removed from the pre-mRNA and the remaining exons connected to re-form a single continuous molecule.
PMID: 14559993. SRrp86 is a unique member of the SR protein superfamily containing one RNA recognition motif and two serine-arginine (SR)-rich domains separated by an unusual glutamic acid-lysine (EK)-rich region. Previously, we showed that SRrp86 could regulate alternative splicing by both positively and negatively modulating the activity of other SR proteins and that the unique EK domain could inhibit both constitutive and alternative splicing. These functions were most consistent with the model in which SRrp86 functions by interacting with and thereby modulating the activity of target proteins. To identify the specific proteins that interact with SRrp86, we used a yeast two-hybrid library screen and immunoprecipitation coupled to mass spectrometry. We show that SRrp86 interacts with all of the core SR proteins, as well as a subset of other splicing regulatory proteins, including SAF-B, hnRNP G, YB-1, and p72. In contrast to previous results that showed activation of SRp20 by SRrp86, we now show that SAF-B, hnRNP G, and 9G8 all antagonize the activity of SRrp86. Overall, we conclude that not only does SRrp86 regulate SR protein activity but that it is, in turn, regulated by other splicing factors to control alternative splice site selection.
Professor, Depts. of Medicine and Biochemistry, Microbiology & Immunology
University of Ottawa
Career Scientist, Ottawa Regional Cancer Centre
Associate Scientist, The Ottawa Hospital Research Institute
Telephone: 613-737-7700 ext 6893
Fax: 613-247-3524
Email: [email protected]
The control of pre-mRNA splicing by the Clk kinase family
We are studying a family of kinases which we believe provide an interface between intracellular signaling networks and the post-transcriptional mechanism of mRNA splicing. We are performing a structure:function analysis of the three Clk family members to identify domains in the three proteins which are involved in regulating splicing. Using homologous recombination we are generating null strains of mice which are lacking one, two or all three Clk genes. The Clk kinases all possess dual specificity kinase activity and yeast expression systems are being used to produce large amounts of the kinase to perform a detailed analysis of the sites of serine, threonine and tyrosine autophosphorylation within the kinase.
CLK2
GeneProduct
CLK4
GeneProduct
CPSF4
GeneProduct
CUGBP1
GeneProduct
DDX20
GeneProduct
DICER1
GeneProduct
FUSIP1
GeneProduct
FUSI MOUSE PMID: 11684676
GMP
Metabolite
HNRPA2B1
GeneProduct
HNRPA3P1
GeneProduct
HNRPC
GeneProduct
HNRPH1
GeneProduct
HNRPH2
GeneProduct
HNRPK
GeneProduct
HNRPU
GeneProduct
HRMT1L1
GeneProduct
NCBP2
GeneProduct
NONO
GeneProduct
PAPOLA
GeneProduct
PCBP2
GeneProduct
PRPF4B
GeneProduct
PSKH1
GeneProduct
PMID: 12466556
PTBP2
GeneProduct
RBMX
GeneProduct
RNU2
GeneProduct
GenBank sequence: K00027
SF3A3
GeneProduct
SF4
GeneProduct
inferred from: SURP 2, G patch protein, UniProt:O60378
SFRS10
GeneProduct
SFRS14
GeneProduct
SFRS2
GeneProduct
SFRS4
GeneProduct
SFRS5
GeneProduct
SFRS9
GeneProduct
PMID: 12738786, PMID: 12024014 (associated with hnRNP A1 splicing)
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Professor, Depts. of Medicine and Biochemistry, Microbiology & Immunology University of Ottawa Career Scientist, Ottawa Regional Cancer Centre Associate Scientist, The Ottawa Hospital Research Institute Telephone: 613-737-7700 ext 6893 Fax: 613-247-3524 Email: [email protected] The control of pre-mRNA splicing by the Clk kinase family
We are studying a family of kinases which we believe provide an interface between intracellular signaling networks and the post-transcriptional mechanism of mRNA splicing. We are performing a structure:function analysis of the three Clk family members to identify domains in the three proteins which are involved in regulating splicing. Using homologous recombination we are generating null strains of mice which are lacking one, two or all three Clk genes. The Clk kinases all possess dual specificity kinase activity and yeast expression systems are being used to produce large amounts of the kinase to perform a detailed analysis of the sites of serine, threonine and tyrosine autophosphorylation within the kinase.Annotated Interactions
No annotated interactions