6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Protein Synthesis Initiation in Eukaryotic Cells

      ,
      Cold Spring Harbor Perspectives in Biology
      Cold Spring Harbor Laboratory

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="d5197e111">This review summarizes our current understanding of the major pathway for the initiation phase of protein synthesis in eukaryotic cells, with a focus on recent advances. We describe the major scanning or messenger RNA (mRNA) m <sup>7</sup>G cap-dependent mechanism, which is a highly coordinated and stepwise regulated process that requires the combined action of at least 12 distinct translation factors with initiator transfer RNA (tRNA), ribosomes, and mRNAs. We limit our review to studies involving either mammalian or budding yeast cells and factors, as these represent the two best-studied experimental systems, and only include a reference to other organisms where particular insight has been gained. We close with a brief description of what we feel are some of the major unknowns in eukaryotic initiation. </p>

          Related collections

          Most cited references136

          • Record: found
          • Abstract: found
          • Article: not found

          Translational control by 5'-untranslated regions of eukaryotic mRNAs.

          The eukaryotic 5' untranslated region (UTR) is critical for ribosome recruitment to the messenger RNA (mRNA) and start codon choice and plays a major role in the control of translation efficiency and shaping the cellular proteome. The ribosomal initiation complex is assembled on the mRNA via a cap-dependent or cap-independent mechanism. We describe various mechanisms controlling ribosome scanning and initiation codon selection by 5' upstream open reading frames, translation initiation factors, and primary and secondary structures of the 5'UTR, including particular sequence motifs. We also discuss translational control via phosphorylation of eukaryotic initiation factor 2, which is implicated in learning and memory, neurodegenerative diseases, and cancer.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Upstream open reading frames cause widespread reduction of protein expression and are polymorphic among humans.

            Upstream ORFs (uORFs) are mRNA elements defined by a start codon in the 5' UTR that is out-of-frame with the main coding sequence. Although uORFs are present in approximately half of human and mouse transcripts, no study has investigated their global impact on protein expression. Here, we report that uORFs correlate with significantly reduced protein expression of the downstream ORF, based on analysis of 11,649 matched mRNA and protein measurements from 4 published mammalian studies. Using reporter constructs to test 25 selected uORFs, we estimate that uORFs typically reduce protein expression by 30-80%, with a modest impact on mRNA levels. We additionally identify polymorphisms that alter uORF presence in 509 human genes. Finally, we report that 5 uORF-altering mutations, detected within genes previously linked to human diseases, dramatically silence expression of the downstream protein. Together, our results suggest that uORFs influence the protein expression of thousands of mammalian genes and that variation in these elements can influence human phenotype and disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Regulation of cap-dependent translation by eIF4E inhibitory proteins.

              Eukaryotic messenger RNAs contain a modified guanosine, termed a cap, at their 5' ends. Translation of mRNAs requires the binding of an initiation factor, eIF4E, to the cap structure. Here, we describe a family of proteins that through a shared sequence regulate cap-dependent translation. The biological importance of this translational regulation is immense, and affects such processes as cell growth, development, oncogenic transformation and perhaps even axon pathfinding and memory consolidation.
                Bookmark

                Author and article information

                Journal
                Cold Spring Harbor Perspectives in Biology
                Cold Spring Harb Perspect Biol
                Cold Spring Harbor Laboratory
                1943-0264
                December 03 2018
                December 2018
                December 2018
                May 07 2018
                : 10
                : 12
                : a033092
                Article
                10.1101/cshperspect.a033092
                6280705
                29735639
                b3ab859b-d250-4e5a-a0f8-2c8b10b2a921
                © 2018
                History

                Comments

                Comment on this article