Introns in UTRs: Why we should stop ignoring them

Although introns in 5′‐ and 3′‐untranslated regions (UTRs) are found in many protein coding genes, rarely are they considered distinctive entities with specific functions. Indeed, mammalian transcripts with 3′‐UTR introns are often assumed nonfunctional because they are subject to elimination by nonsense‐mediated decay (NMD). Nonetheless, recent findings indicate that 5′‐ and 3′‐UTR intron status is of significant functional consequence for the regulation of mammalian genes. Therefore these features should be ignored no longer.

[1]  S. Mirarab,et al.  Sequence Analysis , 2020, Encyclopedia of Bioinformatics and Computational Biology.

[2]  Alfonso Valencia,et al.  Comparative Proteomics Reveals a Significant Bias Toward Alternative Protein Isoforms with Conserved Structure and Function , 2012, Molecular biology and evolution.

[3]  Bo Torben Porse,et al.  Psd-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2 , 2011, Nature Neuroscience.

[4]  M. Okoniewski,et al.  Autoregulation of the nonsense-mediated mRNA decay pathway in human cells. , 2011, RNA.

[5]  Nicholas T. Ingolia,et al.  Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes , 2011, Cell.

[6]  Lior Pachter,et al.  Identification of novel transcripts in annotated genomes using RNA-Seq , 2011, Bioinform..

[7]  J. Zavadil,et al.  Inhibition of Nonsense-Mediated RNA Decay by the Tumor Microenvironment Promotes Tumorigenesis , 2011, Molecular and Cellular Biology.

[8]  H. Dietz,et al.  Perturbation of thymocyte development in nonsense-mediated decay (NMD)-deficient mice , 2011, Proceedings of the National Academy of Sciences.

[9]  Rachid Karam,et al.  Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay. , 2011, Molecular cell.

[10]  Jonathan M. Mudge,et al.  The Origins, Evolution, and Functional Potential of Alternative Splicing in Vertebrates , 2011, Molecular biology and evolution.

[11]  F. P. Roth,et al.  Genome Analysis Reveals Interplay between 5′UTR Introns and Nuclear mRNA Export for Secretory and Mitochondrial Genes , 2011, PLoS genetics.

[12]  Qun Pan,et al.  Regulation of alternative splicing by the core spliceosomal machinery. , 2011, Genes & development.

[13]  Frederick P. Roth,et al.  Identification of Neuronal RNA Targets of TDP-43-containing Ribonucleoprotein Complexes , 2010, The Journal of Biological Chemistry.

[14]  Klaus Wethmar,et al.  Upstream open reading frames: Molecular switches in (patho)physiology , 2010, BioEssays : news and reviews in molecular, cellular and developmental biology.

[15]  P. Harrison,et al.  Large-Scale Evidence for Conservation of NMD Candidature Across Mammals , 2010, PloS one.

[16]  B. Blencowe,et al.  Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decay , 2010, Proceedings of the National Academy of Sciences.

[17]  S. Salzberg,et al.  NIH Public Access Author Manuscript , 2006 .

[18]  Can Cenik,et al.  Genome-wide functional analysis of human 5' untranslated region introns , 2010, Genome Biology.

[19]  O. Mühlemann,et al.  Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors , 2010, Cellular and Molecular Life Sciences.

[20]  Joonhee Han,et al.  SR proteins in vertical integration of gene expression from transcription to RNA processing to translation. , 2009, Molecular cell.

[21]  Melissa J. Moore,et al.  Pre-mRNA Processing Reaches Back toTranscription and Ahead to Translation , 2009, Cell.

[22]  Tatiana A. Tatusova,et al.  NCBI Reference Sequences: current status, policy and new initiatives , 2008, Nucleic Acids Res..

[23]  Eric T. Wang,et al.  Alternative Isoform Regulation in Human Tissue Transcriptomes , 2008, Nature.

[24]  O. Mühlemann,et al.  Recognition and elimination of nonsense mRNA. , 2008, Biochimica et biophysica acta.

[25]  I. Brierley,et al.  Translational termination-re-initiation in viral systems. , 2008, Biochemical Society transactions.

[26]  Nicholas J. McGlincy,et al.  Alternative splicing resulting in nonsense-mediated mRNA decay: what is the meaning of nonsense? , 2008, Trends in biochemical sciences.

[27]  Lina A. Thoren,et al.  NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements. , 2008, Genes & development.

[28]  B. Blencowe,et al.  Regulation of Multiple Core Spliceosomal Proteins by Alternative Splicing-Coupled Nonsense-Mediated mRNA Decay , 2008, Molecular and Cellular Biology.

[29]  J. Lykke-Andersen,et al.  A Competition between Stimulators and Antagonists of Upf Complex Recruitment Governs Human Nonsense-Mediated mRNA Decay , 2008, PLoS biology.

[30]  C. Plass,et al.  The functional consequences of alternative promoter use in mammalian genomes. , 2008, Trends in genetics : TIG.

[31]  F. He,et al.  Association of yeast Upf1p with direct substrates of the NMD pathway , 2007, Proceedings of the National Academy of Sciences.

[32]  Teruyoshi Hishiki,et al.  The H-Invitational Database (H-InvDB), a comprehensive annotation resource for human genes and transcripts , 2007, Nucleic Acids Res..

[33]  T. Rapoport,et al.  The Signal Sequence Coding Region Promotes Nuclear Export of mRNA , 2007, PLoS biology.

[34]  Ed Hurt,et al.  Exporting RNA from the nucleus to the cytoplasm , 2007, Nature Reviews Molecular Cell Biology.

[35]  L. Maquat,et al.  Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function. , 2007, Genes & development.

[36]  Gene W. Yeo,et al.  The EJC Factor eIF4AIII Modulates Synaptic Strength and Neuronal Protein Expression , 2007, Cell.

[37]  Douglas L Black,et al.  A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. , 2007, Genes & development.

[38]  S. Brenner,et al.  Unproductive splicing of SR genes associated with highly conserved and ultraconserved DNA elements , 2007, Nature.

[39]  Tyson A. Clark,et al.  Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay. , 2007, Genes & development.

[40]  R. Reed,et al.  Human mRNA Export Machinery Recruited to the 5′ End of mRNA , 2006, Cell.

[41]  Douglas G Scofield,et al.  Intron size, abundance, and distribution within untranslated regions of genes. , 2006, Molecular biology and evolution.

[42]  J. Thierry-Mieg,et al.  AceView: a comprehensive cDNA-supported gene and transcripts annotation , 2006, Genome Biology.

[43]  E. Birney,et al.  EGASP: the human ENCODE Genome Annotation Assessment Project , 2006, Genome Biology.

[44]  Martin S. Taylor,et al.  Genome-wide analysis of mammalian promoter architecture and evolution , 2006, Nature Genetics.

[45]  E. Hol,et al.  hUPF2 Silencing Identifies Physiologic Substrates of Mammalian Nonsense-Mediated mRNA Decay , 2006, Molecular and Cellular Biology.

[46]  G. Dreyfuss,et al.  Binding of a novel SMG-1-Upf1-eRF1-eRF3 complex (SURF) to the exon junction complex triggers Upf1 phosphorylation and nonsense-mediated mRNA decay. , 2006, Genes & development.

[47]  B. Frey,et al.  Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression. , 2006, Genes & development.

[48]  Eric W. Deutsch,et al.  The PeptideAtlas project , 2005, Nucleic Acids Res..

[49]  M. Cuccurese,et al.  Alternative splicing and nonsense-mediated mRNA decay regulate mammalian ribosomal gene expression , 2005, Nucleic acids research.

[50]  P. Green,et al.  Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Seiji Masuda,et al.  Recruitment of the human TREX complex to mRNA during splicing. , 2005, Genes & development.

[52]  L. Maquat,et al.  Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. , 2005, Current opinion in cell biology.

[53]  Graziano Pesole,et al.  uAUG and uORFs in human and rodent 5'untranslated mRNAs. , 2005, Gene.

[54]  J. Steitz,et al.  SRprises along a messenger's journey. , 2005, Molecular cell.

[55]  T. Hubbard,et al.  The Vertebrate Genome Annotation (Vega) database , 2004, Nucleic Acids Res..

[56]  Robertson Craig,et al.  Open source system for analyzing, validating, and storing protein identification data. , 2004, Journal of proteome research.

[57]  Francisco Martinez-Murillo,et al.  Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise , 2004, Nature Genetics.

[58]  M. Moore,et al.  The ever-increasing complexities of the exon junction complex. , 2004, Current opinion in cell biology.

[59]  Noboru Jo Sakabe,et al.  Detection and evaluation of intron retention events in the human transcriptome. , 2004, RNA.

[60]  S. Brenner,et al.  An unappreciated role for RNA surveillance , 2004, Genome Biology.

[61]  J. McCarthy,et al.  Regulation of fungal gene expression via short open reading frames in the mRNA 5′untranslated region , 2003, Molecular microbiology.

[62]  M. Moore,et al.  A quantitative analysis of intron effects on mammalian gene expression. , 2003, RNA.

[63]  H. Le Hir,et al.  How introns influence and enhance eukaryotic gene expression. , 2003, Trends in biochemical sciences.

[64]  S. Brenner,et al.  Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Jurg Ott,et al.  Distribution and characterization of regulatory elements in the human genome. , 2002, Genome research.

[66]  A. Furger,et al.  Promoter proximal splice sites enhance transcription. , 2002, Genes & development.

[67]  G. Dreyfuss,et al.  Translation Is Required to Remove Y14 from mRNAs in the Cytoplasm , 2002, Current Biology.

[68]  Jun Wang,et al.  A Quality Control Pathway That Down-regulates Aberrant T-cell Receptor (TCR) Transcripts by a Mechanism Requiring UPF2 and Translation* , 2002, The Journal of Biological Chemistry.

[69]  Kevin Struhl,et al.  TREX is a conserved complex coupling transcription with messenger RNA export , 2002, Nature.

[70]  L. Maquat,et al.  Evidence for a Pioneer Round of mRNA Translation mRNAs Subject to Nonsense-Mediated Decay in Mammalian Cells Are Bound by CBP80 and CBP20 , 2001, Cell.

[71]  H. Le Hir,et al.  The exon–exon junction complex provides a binding platform for factors involved in mRNA export and nonsense‐mediated mRNA decay , 2001, The EMBO journal.

[72]  A Sureau,et al.  SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs , 2001, The EMBO journal.

[73]  J. Mendell,et al.  Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability. , 2001, Human molecular genetics.

[74]  H. Le Hir,et al.  The spliceosome deposits multiple proteins 20–24 nucleotides upstream of mRNA exon–exon junctions , 2000, The EMBO journal.

[75]  Q. Mitrovich,et al.  Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans. , 2000, Genes & development.

[76]  H. Le Hir,et al.  Pre-mRNA splicing alters mRNP composition: evidence for stable association of proteins at exon-exon junctions. , 2000, Genes & development.

[77]  L. Maquat,et al.  Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm. , 1998, RNA.

[78]  L. Maquat,et al.  A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. , 1998, Trends in biochemical sciences.

[79]  K. Wassarman,et al.  Nuclear history of a pre‐mRNA determines the translational activity of cytoplasmic mRNA , 1998, The EMBO journal.

[80]  S. Amara,et al.  Alternative RNA processing: determining neuronal phenotype. , 1984, Science.

[81]  J. Cáceres,et al.  The SR protein family of splicing factors: master regulators of gene expression. , 2009, The Biochemical journal.

[82]  S. Lehnart,et al.  Why Do We Still Have a Maternally Inherited Mitochondrial DNA ? Insights from Evolutionary Medicine , 2007 .

[83]  N. Sakabe,et al.  transcriptome Detection and evaluation of intron retention events in the human , 2004 .

[84]  M. Diekhans,et al.  BIOINFORMATICS ORIGINAL PAPER Genome analysis The UCSC Known Genes , 2022 .