title: mRNA length-sensing in eukaryotic translation: reconsidering the "closed loop" and its implications for translational control.
abstract: Most eukaryotic mRNAs are recruited to the ribosome by recognition of a 5' m7GpppN cap. 30 years of genetic and biochemical evidence point to a role for interaction between the 5' cap-interacting factors and the 3' poly(A)-binding protein in bringing the ends of the mRNA into close proximity and promoting both translation and stability of the mRNA, in a form known as the "closed loop". However, the results of recent RNA-protein interaction studies suggest that not all mRNAs have equal access to the closed loop factors. Furthermore, association with closed loop factors appears to be highly biased towards mRNAs with short open reading frames, echoing the trend for higher translation of short mRNAs that has been observed in many eukaryotes. We recently reported that the ribosomal signaling scaffold protein RACK1 promotes the efficient translation of short mRNAs that strongly associate with the closed loop factors. Here, we discuss the implications of these observations with respect to translational control and suggest avenues through which the universality of the closed loop in eukaryotic translation could be revisited.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, USA.|Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Thompson
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, USA. wgilbert@mit.edu.|Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06510, USA. wgilbert@mit.edu.
authors.forename: Wendy V
authors.initials: WV
authors.lastname: Gilbert
mesh_terms: D005057:Eukaryotic Cells; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D012269:Ribosomal Proteins / Q000235:genetics; D012270:Ribosomes / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D012269:Ribosomal Proteins
keywords: Closed loop; RACK1; Ribosome; Translation