NORMAL GENOMIC

• Abramovich C, Yakobson B, Chebath J, Revel M
• A protein-arginine methyltransferase binds to the intracytoplasmic domainof the IFNAR1 chain in the type I interferon receptor.
• EMBO J. 1997; 16: 260-6
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• The intracytoplasmic domain (IC) of cytokine receptors provides dockingsites for proteins which mediate signal transduction. Thus, ininterferon-alpha,beta receptors (IFNAR1 and 2), the IC region bindsprotein-tyrosine and -serine/threonine kinases which phosphorylate thereceptor and the associated Stat transcription factors. A two-hybridscreening was carried out to identify additional proteins which couldinteract with the IC domain of the IFNAR1 chain of the IFN-alpha,betareceptor. Several positive clones representing a protein sequencedesignated IR1B4 were recovered from a human cDNA library. IR1B4 wasidentified as the human homolog of PRMT1, a protein-argininemethyltransferase from rat cells. Flag-IR1B4 fusion proteins bind to theisolated IFNAR1 intracytoplasmic domain produced in Escherichia coli, aswell as to the intact IFNAR1 chain extracted by detergent from human U266cell membranes. S-Adenosylmethionine-dependent methyltransferase activitywas precipitated by anti-IFNAR1 antibodies from untreated human cells.IR1B4/PRMT1 is involved in IFN action since U266 cells rendered deficientin this methyltransferase by antisense oligonucleotides become moreresistant to growth inhibition by IFN. Methylation of proteins by enzymeswhich can attach to the IC domains of receptors may be a signalingmechanism complementing protein phosphorylation. Among substratesmethylated by PRMT1 are RNA-binding heterogeneous nuclearribonucleoproteins (hnRNPs) which are involved in mRNA processing,splicing and transport into the cytoplasm.

• Jahner D, Hunter T
• The ras-related gene rhoB is an immediate-early gene inducible by v-Fps,epidermal growth factor, and platelet-derived growth factor in ratfibroblasts.
• Mol Cell Biol. 1991; 11: 3682-90
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• A set of genes is rapidly inducible when quiescent fibroblasts arestimulated by growth factors or by the activation of temperature-sensitiveretroviral protein-tyrosine kinases. Most of these so-calledimmediate-early genes were cloned by differential cDNA hybridization. DNAsequence analysis identified many of them as putative members of thegrowth factor or of the transcription factor gene family, suggesting arole in signal transmission during the G0-to-G1 transition. In this study,we identified one of the genes that are rapidly inducible by theretroviral protein-tyrosine kinases v-Src and v-Fps of Rous sarcoma virusand Fujinami sarcoma virus, respectively, as the rhoB gene, a member ofthe ras gene superfamily whose products are GTP-binding proteins, rhoB istransiently activated at the transcriptional level by v-Fps and byepidermal growth factor. Its labile RNA is inducible in the presence ofcycloheximide but not of actinomycin D. rhoB is strongly induced byepidermal growth factor and by platelet-derived growth factor both insubconfluent, serum-starved and in density-arrested Rat-2 fibroblasts.Fetal calf serum is a poor inducer, particularly in density-arrestedcells, and phorbol esters do not increase rhoB expression at all. Thesedata suggest that rhoB is inducible by protein-tyrosine kinases through apathway not involving the activation of protein kinase C. Neither theclosely related rhoC and rhoA genes nor the distantly related c-H-ras geneis rapidly inducible by mitogens. Thus, rhoB is the first known member ofthe small GTP-binding proteins among the immediate-early genes.

• Bonnieu A, Roux P, Marty L, Jeanteur P, Piechaczyk M
• AUUUA motifs are dispensable for rapid degradation of the mouse c-myc RNA.
• Oncogene. 1990; 5: 1585-8
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• Sequence determinants responsible for c-myc RNA rapid turn-over arelocalized within the 3' non-coding region which is mainly characterized bythe presence of two polyadenylation signals and a high content in A and U.Although the AUUUA/UUAUUUA motif is commonly thought to specify a wholeclass of unstable RNAs coding for various onco-proteins and cytokines,site-directed mutagenesis showed that both of the two such sequences foundin the mouse c-myc RNA are dispensable for rapid RNA degradation. Althoughless efficient than the whole 3' non-coding region, the last 50nucleotides of c-myc RNA, mainly made up of U and A and devoid ofAUUUA/UUAUUUA motif, are sufficient to confer instability to the codingsequence.