122 research outputs found

    Inside Maine Books piece on Slipknot, the first in a series of Jane Bunker m

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    Inside Maine Books piece on Slipknot, the first in a series of Jane Bunker mysteries by Isle au Haut author Linda Greenlaw. With a brief note on Kilt Dead, the first Liss MacCrimmon mystery by Western Maine writer Kathy Lynn Emerson, under the pseudonym Kaitlyn Dunnett

    The human insulin receptor mRNA contains a functional internal ribosome entry segment

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    Regulation of mRNA translation is an important mechanism determining the level of expression of proteins in eukaryotic cells. Translation is most commonly initiated by cap-dependent scanning, but many eukaryotic mRNAs contain internal ribosome entry segments (IRESs), providing an alternative means of initiation capable of independent regulation. Here, we show by using dicistronic luciferase reporter vectors that the 5'-UTR of the mRNA encoding human insulin receptor (hIR) contains a functional IRES. RNAi-mediated knockdown showed that the protein PTB was required for maximum IRES activity. Electrophoretic mobility shift assays confirmed that PTB1, PTB2 and nPTB, but not unr or PTB4, bound to hIR mRNA, and deletion mapping implicated a CCU motif 448 nt upstream of the initiator AUG in PTB binding. The IR-IRES was functional in a number of cell lines, and most active in cells of neuronal origin, as assessed by luciferase reporter assays. The IRES was more active in confluent than sub-confluent cells, but activity did not change during differentiation of 3T3-L1 fibroblasts to adipocytes. IRES activity was stimulated by insulin in sub-confluent cells. The IRES may function to maintain expression of IR protein in tissues such as the brain where mRNA translation by cap-dependent scanning is less effective

    Grammatical properties of pronouns and their representation : an exposition

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    This volume brings together a cross-section of recent research on the grammar and representation of pronouns, centering around the typology of pronominal paradigms, the generation of syntactic and semantic representations for constructions containing pronouns, and the neurological underpinnings for linguistic distinctions that are relevant for the production and interpretation of these constructions. In this introductory chapter we first give an exposition of our topic (section 2). Taking the interpretation of pronouns as a starting point, we discuss the basic parameters of pronominal representations, and draw a general picture of how morphological, semantic, discourse-pragmatic and syntactic aspects come together. In section 3, we sketch the different domains of research that are concerned with these phenomena, and the particular questions they are interested in, and show how the papers in the present volume fit into the picture. Section 4 gives summaries of the individual papers, and a short synopsis of their main points of convergence

    Canonical Initiation Factor Requirements of the Myc Family of Internal Ribosome Entry Segments

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    Initiation of protein synthesis in eukaryotes requires recruitment of the ribosome to the mRNA and its translocation to the start codon. There are at least two distinct mechanisms by which this process can be achieved; the ribosome can be recruited either to the cap structure at the 5' end of the message or to an internal ribosome entry segment (IRES), a complex RNA structural element located in the 5' untranslated region (5'-UTR) of the mRNA. However, it is not well understood how cellular IRESs function to recruit the ribosome or how the 40S ribosomal subunits translocate from the initial recruitment site on the mRNA to the AUG initiation codon. We have investigated the canonical factors that are required by the IRESs found in the 5'-UTRs of c-, L-, and N-myc, using specific inhibitors and a tissue culture-based assay system, and have shown that they differ considerably in their requirements. The L-myc IRES requires the eIF4F complex and the association of PABP and eIF3 with eIF4G for activity. The minimum requirements of the N- and c-myc IRESs are the C-terminal domain of eIF4G to which eIF4A is bound and eIF3, although interestingly this protein does not appear to be recruited to the IRES RNA via eIF4G. Finally, our data show that all three IRESs require a ternary complex, although in contrast to c- and L-myc IRESs, the N-myc IRES has a lesser requirement for a ternary comple
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