Biomaterial Database

A discrete 3' region of U6 small nuclear RNA modulates the phosphorylation cycle of the C1 heterogeneous nuclear ribonucleoprotein particle protein. 1996

S H Mayrand, and P A Fung, and T Pederson

Cell Biology Group, Worcester Foundation for Biomedical Research, Shrewsbury, Massachusetts 01545, USA.

The C heterogeneous ribonucleoprotein particle (hnRNP) protein bind to nascent pre-mRNA and may participate in assembly of the early prespliceosome. Ser/Thr phosphorylation of the C1 hnRNP protein in HeLa nuclear extracts regulates its binding to pre-mRNA (S. H. Mayrand, P. Dwen, and T. Pederson, Proc. Natl. Acad. Sci. USA 90:7764-7768, 1993). We have now further investigated the phosphorylation cycle of the C1 hnRNP protein, with emphasis on its regulation. Pretreatment of nuclear extracts with micrococcal nuclease eliminated the phosphorylation of C1 hnRNP protein, but pretreatment with DNase did not, suggesting a dependence on RNA. Oligodeoxynucleotide-targeted RNase H cleavage of U1, U2, and U4 small nuclear RNAs did not affect the phosphorylation of C1 hnRNP protein. However, cleavage of nucleotides 78 to 95, but not other regions, of U6 small nuclear RNA resulted in an inhibition of the dephosphorylation step of the C1 hnRNP protein phosphorylation cycle. This inhibition was as pronounced as that seen with the serine/threonine protein phosphatase inhibitor okadaic acid. C1 hnRNP protein dephosphorylation could be completely restored by the addition of intact U6 RNA. Add-back experiments with mutant RNAs further delineated the minimal region essential for C1 protein dephosphorylation as residing in nucleotides 85 to 92 of U6 RNA. These results illuminate a hitherto unanticipated function of U6 RNA: the modulation of a phosphorylation-dephosphorylation cycle of C1 hnRNP protein that influences the binding affinity of this protein for pre-mRNA. This newly revealed function of U6 RNA is likely to play a very early role in the prespliceosome assembly pathway, prior to U6 RNA's entry into the mature spliceosome's active center.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D006367	HeLa Cells	The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays.	Cell, HeLa,Cells, HeLa,HeLa Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001483	Base Sequence	The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.	DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D012261	Ribonucleoproteins	Complexes of RNA-binding proteins with ribonucleic acids (RNA).	Ribonucleoprotein
D012342	RNA, Small Nuclear	Short chains of RNA (100-300 nucleotides long) that are abundant in the nucleus and usually complexed with proteins in snRNPs (RIBONUCLEOPROTEINS, SMALL NUCLEAR). Many function in the processing of messenger RNA precursors. Others, the snoRNAs (RNA, SMALL NUCLEOLAR), are involved with the processing of ribosomal RNA precursors.	Low Molecular Weight Nuclear RNA,Small Nuclear RNA,snRNA,Chromatin-Associated RNA,Small Molecular Weight RNA,Chromatin Associated RNA,RNA, Chromatin-Associated
D017421	Sequence Analysis	A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information.	Sequence Determination,Analysis, Sequence,Determination, Sequence,Determinations, Sequence,Sequence Determinations,Analyses, Sequence,Sequence Analyses
D034441	Heterogeneous-Nuclear Ribonucleoproteins	A family of ribonucleoproteins that were originally found as proteins bound to nascent RNA transcripts in the form of ribonucleoprotein particles. Although considered ribonucleoproteins they are primarily classified by their protein component. They are involved in a variety of processes such as packaging of RNA and RNA TRANSPORT within the nucleus. A subset of heterogeneous-nuclear ribonucleoproteins are involved in additional functions such as nucleocytoplasmic transport (ACTIVE TRANSPORT, CELL NUCLEUS) of RNA and mRNA stability in the CYTOPLASM.	Heterogeneous Nuclear Ribonucleoprotein,Informatin,Informofer,hnRNP,hnRNP Complexes,hnRNP Particles,hnRNP Proteins,Complexes, hnRNP,Heterogeneous Nuclear Ribonucleoproteins,Nuclear Ribonucleoprotein, Heterogeneous,Particles, hnRNP,Ribonucleoprotein, Heterogeneous Nuclear,Ribonucleoproteins, Heterogeneous-Nuclear
D034482	Heterogeneous-Nuclear Ribonucleoprotein Group C	A group of closely related heterogeneous-nuclear ribonucleoproteins of approximately 41-43 kDa in size found in the cell nucleus. Members of this class have been implicated in a variety of processes including splicing, polyadenylation, and nuclear retention of RNA.	C-Type Protein HnRNP,HNRNP C Protein,Heterogeneous-Nuclear Ribonucleoprotein C,Heterogeneous-Nuclear Ribonucleoprotein Type C1-C2,hnRNP C Proteins,hnRNP C1-C2 Proteins,Heterogeneous Nuclear Ribonucleoprotein C,Heterogeneous Nuclear Ribonucleoprotein Group C,Heterogeneous Nuclear Ribonucleoprotein Type C1 C2,Ribonucleoprotein C, Heterogeneous-Nuclear,hnRNP C1 C2 Proteins