reading frames


Summary: The three possible sequences of CODONS by which GENETIC TRANSLATION may occur from one nucleotide sequence. A segment of mRNA 5'AUCCGA3' could be translated as 5'AUC.. or 5'UCC.. or 5'CCG.., depending on the location of the START CODON.

Top Publications

  1. Wang J, Chang Y, Hamilton J, Wilkinson M. Nonsense-associated altered splicing: a frame-dependent response distinct from nonsense-mediated decay. Mol Cell. 2002;10:951-7 pubmed
    ..Our results suggest that NAS and NMD are distinct mechanisms despite being triggered by the same signal. ..
  2. Aartsma Rus A, van Deutekom J, Fokkema I, van Ommen G, den Dunnen J. Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve. 2006;34:135-44 pubmed
    ..In this study we provide an update of the mutational variability in the DMD gene, particularly focusing on genotype-phenotype correlations and mutations that appear to be exceptions to the reading-frame rule. ..
  3. Zhao X, McGirr K, Buehring G. Potential evolutionary influences on overlapping reading frames in the bovine leukemia virus pXBL region. Genomics. 2007;89:502-11 pubmed
    ..contains a pXBL region encoding the 3' parts of four regulatory proteins (Tax, Rex, G4, R3) in overlapping reading frames. Here we report the pXBL polymorphisms of 30 isolates from four countries...
  4. Ahmed Z, Masmoudi S, Kalay E, Belyantseva I, Mosrati M, Collin R, et al. Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans. Nat Genet. 2008;40:1335-40 pubmed publisher
    ..3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, detected by protein blot analyses...
  5. Urbonavicius J, Qian Q, Durand J, Hagervall T, Bj rk G. Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO J. 2001;20:4863-73 pubmed publisher
    ..We propose that the improvement of reading frame maintenance has been and is the major selective factor for the emergence of new modified nucleosides...
  6. Zacchi P, Sblattero D, Florian F, Marzari R, Bradbury A. Selecting open reading frames from DNA. Genome Res. 2003;13:980-90 pubmed
    We describe a method to select DNA encoding functional open reading frames (ORFs) from noncoding DNA within the context of a specific vector...
  7. Chapdelaine P, Pichavant C, Rousseau J, Pâques F, Tremblay J. Meganucleases can restore the reading frame of a mutated dystrophin. Gene Ther. 2010;17:846-58 pubmed publisher
    ..New MGNs engineered to target a sequence including or near nonsense mutation could also be used to delete it. ..
  8. Kovacs E, Tompa P, Liliom K, Kalmar L. Dual coding in alternative reading frames correlates with intrinsic protein disorder. Proc Natl Acad Sci U S A. 2010;107:5429-34 pubmed publisher
    ..By discussing several examples, we demonstrate that dual coding may be an effective mechanism for the evolutionary appearance of novel intrinsically disordered regions with new functions. ..
  9. Spitali P, Rimessi P, Fabris M, Perrone D, Falzarano S, Bovolenta M, et al. Exon skipping-mediated dystrophin reading frame restoration for small mutations. Hum Mutat. 2009;30:1527-34 pubmed publisher
    ..This behavior may be related to the effect of the mutations on exon skipping propensity, and highlights the complexity of identifying optimal AONs for skipping exons with small mutations. ..

More Information


  1. Stallmeyer B, Drugeon G, Reiss J, Haenni A, Mendel R. Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames. Am J Hum Genet. 1999;64:698-705 pubmed
    ..shows a bicistronic structure, encoding the small and large subunits of the MPT-synthase in two different open reading frames (ORFs) that overlap by 77 nucleotides...
  2. Goldman E, Korus M, Mandecki W. Efficiencies of translation in three reading frames of unusual non-ORF sequences isolated from phage display. FASEB J. 2000;14:603-11 pubmed
    ..These sequences have been cloned in all three reading frames relative to the reporter...
  3. Nasvall S, Nilsson K, Bjork G. The ribosomal grip of the peptidyl-tRNA is critical for reading frame maintenance. J Mol Biol. 2009;385:350-67 pubmed publisher
    ..We suggest that the "ribosomal grip" of the peptidyl-tRNA is pivotal for maintaining the reading frame. ..
  4. Resch A, Xing Y, Alekseyenko A, Modrek B, Lee C. Evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation. Nucleic Acids Res. 2004;32:1261-9 pubmed
    ..These data indicate that a subpopulation of modern alternative splicing events was present in the common ancestors of these genomes, and was under functional selection pressure to preserve the protein reading frame. ..
  5. Schwab S, Shugart J, Horng T, Malarkannan S, Shastri N. Unanticipated antigens: translation initiation at CUG with leucine. PLoS Biol. 2004;2:e366 pubmed
    ..These peptides are derived from not only conventional but also cryptic translational reading frames, including some without conventional AUG codons...
  6. Yewdell J. Immunology. Hide and seek in the peptidome. Science. 2003;301:1334-5 pubmed
  7. Schirmbeck R, Riedl P, Fissolo N, Lemonnier F, Bertoletti A, Reimann J. Translation from cryptic reading frames of DNA vaccines generates an extended repertoire of immunogenic, MHC class I-restricted epitopes. J Immunol. 2005;174:4647-56 pubmed
    ..Human CMV promoter-driven Pol constructs encoding different Pol fragments in primary or alternative reading frames elicited comparable levels of Pol3-specific T cell responses...
  8. Klase Z, Donio M, Blauvelt A, Marx P, Jeang K, Smith S. A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL) vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames. Retrovirology. 2006;3:1 pubmed publisher
    ..if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins...
  9. Rogic S, Ouellette B, Mackworth A. Improving gene recognition accuracy by combining predictions from two gene-finding programs. Bioinformatics. 2002;18:1034-45 pubmed
    ..0% and exon level specificity by 32.5% compared to the best result obtained by either of the two programs individually. The scripts implementing our methods are available from ..
  10. Marquez V, Wilson D, Tate W, Triana Alonso F, Nierhaus K. Maintaining the ribosomal reading frame: the influence of the E site during translational regulation of release factor 2. Cell. 2004;118:45-55 pubmed
    ..Consistently, in a minimal system, the presence of the E site tRNA prevents the +1 frameshift event, illustrating the importance of the E site for reading-frame maintenance. ..
  11. Maness N, Wilson N, Reed J, Piaskowski S, Sacha J, Walsh A, et al. Robust, vaccine-induced CD8(+) T lymphocyte response against an out-of-frame epitope. J Immunol. 2010;184:67-72 pubmed publisher
    ..Our data demonstrate both that the pathway from vaccination to immune response is not well understood and that products of alternate reading frames may be rich and untapped sources of T cell epitopes.
  12. Seligmann H. The ambush hypothesis at the whole-organism level: Off frame, 'hidden' stops in vertebrate mitochondrial genes increase developmental stability. Comput Biol Chem. 2010;34:80-5 pubmed publisher
    ..Results suggest adaptive rather than neutralist interpretations of the ambush hypothesis. ..
  13. Sanders C, Curran J. Genetic analysis of the E site during RF2 programmed frameshifting. RNA. 2007;13:1483-91 pubmed
    ..These findings indicate that pairing between the deacyl-tRNA and the E-site codon opposes frameshifting. We discuss the implications of these findings on frame maintenance and on the RF2 programmed frameshift mechanism. ..
  14. Harger J, Meskauskas A, Dinman J. An "integrated model" of programmed ribosomal frameshifting. Trends Biochem Sci. 2002;27:448-54 pubmed
  15. Ho O, Green W. Cytolytic CD8+ T cells directed against a cryptic epitope derived from a retroviral alternative reading frame confer disease protection. J Immunol. 2006;176:2470-5 pubmed
    ..epitopes," defined by their nontraditional methods of generation, including derivation from alternative reading frames (ARFs)...
  16. Jenner L, Demeshkina N, Yusupova G, Yusupov M. Structural aspects of messenger RNA reading frame maintenance by the ribosome. Nat Struct Mol Biol. 2010;17:555-60 pubmed publisher
    ..These data allow rationalization of how modification deficiencies of ms(2)i(6)A37 in tRNAs may lead to shifts of the translational reading frame...
  17. Baranov P, Gesteland R, Atkins J. P-site tRNA is a crucial initiator of ribosomal frameshifting. RNA. 2004;10:221-30 pubmed
    ..This model offers an alternative explanation to previously published mechanisms of programmed frameshifting, such as out-of-frame tRNA binding, and a different perspective on simultaneous tandem tRNA slippage. ..
  18. Yokota T, Hoffman E, Takeda S. Antisense oligo-mediated multiple exon skipping in a dog model of duchenne muscular dystrophy. Methods Mol Biol. 2011;709:299-312 pubmed publisher
  19. Quelle D, Zindy F, Ashmun R, Sherr C. Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell. 1995;83:993-1000 pubmed
    ..Economical reutilization of coding sequences in this manner is practically without precedent in mammalian genomes, and the unitary inheritance of p16INK4a and p19ARF may underlie their dual requirement in cell cycle control. ..
  20. Cardinaud S, Moris A, Février M, Rohrlich P, Weiss L, Langlade Demoyen P, et al. Identification of cryptic MHC I-restricted epitopes encoded by HIV-1 alternative reading frames. J Exp Med. 2004;199:1053-63 pubmed
    ..MHC) I-restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides...
  21. Anson D, Dunning K. Codon-optimized reading frames facilitate high-level expression of the HIV-1 minor proteins. Mol Biotechnol. 2005;31:85-8 pubmed
    We have constructed reading frames for the HIV-1 YU-2 minor proteins Vpr, Vpu, Vif and Nef that are codon-optimized for high-level expression in mammalian cells...
  22. Villesen P, Aagaard L, Wiuf C, Pedersen F. Identification of endogenous retroviral reading frames in the human genome. Retrovirology. 2004;1:32 pubmed
    ..encoded genes are degenerate due to mutational decay and only a few non-HERV-K loci are known to retain intact reading frames. Additional intact HERV genes may exist, since retroviral reading frames have not been systematically ..
  23. Rousseau J, Chapdelaine P, Boisvert S, Almeida L, Corbeil J, Montpetit A, et al. Endonucleases: tools to correct the dystrophin gene. J Gene Med. 2011;13:522-37 pubmed publisher
    ..Endonucleases could thus be used to treat Duchenne muscular dystrophy and other hereditary diseases that are the result of a nonsense codon or a frame shift mutation. ..
  24. Graddis T, Diegel M, McMahan C, Tsavler L, Laus R, Vidovic D. Tumor immunotherapy with alternative reading frame peptide antigens. Immunobiology. 2004;209:535-44 pubmed
    ..The strategy described here has potential for designing highly efficient novel vaccines for Ag-specific immunotherapy of human malignancies. ..
  25. Li D, Pakala S, Reddy S, Ohshiro K, Zhang J, Wang L, et al. Bidirectional autoregulatory mechanism of metastasis-associated protein 1-alternative reading frame pathway in oncogenesis. Proc Natl Acad Sci U S A. 2011;108:8791-6 pubmed publisher
  26. Underhill D, Vogan K, Gros P. Analysis of the mouse Splotch-delayed mutation indicates that the Pax-3 paired domain can influence homeodomain DNA-binding activity. Proc Natl Acad Sci U S A. 1995;92:3692-6 pubmed
    ..Furthermore, it is apparent that the paired domain and homeodomain of Pax-3 do not function as independent domains, since a mutation in the former impairs the DNA-binding activity of the latter. ..
  27. Imafuku I, Waragai M, Takeuchi S, Kanazawa I, Kawabata M, Mouradian M, et al. Polar amino acid-rich sequences bind to polyglutamine tracts. Biochem Biophys Res Commun. 1998;253:16-20 pubmed
    ..Three of these clones could form polar helical structures. These observations suggest that polar amino acid-rich sequences are essential for binding to the polyglutamine tract. ..
  28. Toyokawa G, Takenoyama M, Taguchi K, Arakaki K, Inamasu E, Toyozawa R, et al. The first case of lung carcinosarcoma harboring in-frame deletions at exon19 in the EGFR gene. Lung Cancer. 2013;81:491-4 pubmed publisher
    ..Although carcinosarcoma is a rare malignancy of the lungs, genetic analyses of oncogenic drivers, such as the EGFR gene, should be conducted. ..
  29. Mével Ninio M, Fouilloux E, Guenal I, Vincent A. The three dominant female-sterile mutations of the Drosophila ovo gene are point mutations that create new translation-initiator AUG codons. Development. 1996;122:4131-8 pubmed
    ..We propose that premature expression of long Ovo protein isoforms occurs in ovoD mutants and interferes with wild-type Ovo function in controlling female germline differentiation. ..
  30. Maier C, Maier R, Hintner H, Bauer J, Onder K. Coupled yeast 2-hybrid-mammalian 2-hybrid reading-frame-independent and site-specific recombinational cloning vector system. Assay Drug Dev Technol. 2010;8:625-9 pubmed publisher
  31. Manco L, Pereira J, Relvas L, Rebelo U, Crisóstomo A, Bento C, et al. Chronic hemolytic anemia is associated with a new glucose-6-phosphate dehydrogenase in-frame deletion in an older woman. Blood Cells Mol Dis. 2011;46:288-93 pubmed publisher
    ..This observation indicates that HUMARA assay in women should be assessed in granulocytes and not in total leukocytes. ..
  32. Ho J, Lin T, Li C, Lee A, Cheng A, Chen M, et al. Functions of some capsular polysaccharide biosynthetic genes in Klebsiella pneumoniae NTUH K-2044. PLoS ONE. 2011;6:e21664 pubmed publisher
    ..Taken together, the results suggest that kp3706, kp3709 or kp3712 genes are strongly related to the pathogenesis of K. pneumoniae K1. ..
  33. Liu Z, Diaz L, Haas A, Giudice G. cDNA cloning of a novel human ubiquitin carrier protein. An antigenic domain specifically recognized by endemic pemphigus foliaceus autoantibodies is encoded in a secondary reading frame of this human epidermal transcript. J Biol Chem. 1992;267:15829-35 pubmed
    ..epitope and the ubiquitin carrier protein were shown to be encoded in two different translational reading frames. The relevance of the cloned EPF epitope in the pathogenesis of this autoimmune disorder remains to be ..
  34. Nambiar P, Giardina C, Guda K, Aizu W, Raja R, Rosenberg D. Role of the alternating reading frame (P19)-p53 pathway in an in vivo murine colon tumor model. Cancer Res. 2002;62:3667-74 pubmed
    ..The AOM colon cancer model may be well suited for studying tumor promotion events that precede p53 disruption. ..
  35. Wordeman L, Mitchison T. Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biol. 1995;128:95-104 pubmed
    ..1992). MCAK protein is present in interphase and mitotic CHO cells and is transcribed as a single 3.4-kb message...
  36. Starck S, Shastri N. Non-conventional sources of peptides presented by MHC class I. Cell Mol Life Sci. 2011;68:1471-9 pubmed publisher
    ..Intriguingly, MHC I molecules present peptides encoded not only in the primary open reading frames but also those encoded in alternate reading frames...
  37. Wang W, Xue Y, Zhou S, Kuo A, Cairns B, Crabtree G. Diversity and specialization of mammalian SWI/SNF complexes. Genes Dev. 1996;10:2117-30 pubmed
    ..However, the complexes in mammals are more diverse than the SWI/SNF complex in yeast and are likely dedicated to developmentally distinct functions. ..
  38. Hasan M, Yaguchi T, Sugihara T, Kumar P, Taira K, Reddel R, et al. CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53. J Biol Chem. 2002;277:37765-70 pubmed
    ..It co-localizes and interacts with ARF in the nucleolus. We demonstrate that CARF is co-regulated with ARF, cooperates with it in activating p53, and thus acts as a novel component of the ARF-p53-p21 pathway. ..
  39. Datta A, Nag A, Pan W, Hay N, Gartel A, Colamonici O, et al. Myc-ARF (alternate reading frame) interaction inhibits the functions of Myc. J Biol Chem. 2004;279:36698-707 pubmed
    ..Our results strongly suggest that cMyc is a bona fide target of ARF and that ARF attenuates c-Myc independently of the ARF-p53 axis. ..
  40. Huang J, Jiang X, Xia X, Yu A, Mao R, Chen X, et al. Cloning and functional identification of delta5 fatty acid desaturase gene and its 5'-upstream region from marine fungus Thraustochytrium sp. FJN-10. Mar Biotechnol (NY). 2011;13:12-21 pubmed publisher
    ..Preliminary functional analysis of this promoter in S. cerevisiae shows that the 5'-upstream region of fad5 could drive the expression of green fluorescent protein. ..
  41. Jäger G, Nilsson K, Bjork G. The phenotype of many independently isolated +1 frameshift suppressor mutants supports a pivotal role of the P-site in reading frame maintenance. PLoS ONE. 2013;8:e60246 pubmed publisher
    ..The isolation and characterization of the S9 mutants gave strong support of our model that the ribosomal grip of the peptidyl-tRNA is pivotal for the reading frame maintenance. ..
  42. Matsugi J, Murao K, Ishikura H. Effect of B. subtilis TRNA(Trp) on readthrough rate at an opal UGA codon. J Biochem. 1998;123:853-8 pubmed
    ..This suggests that this tRNATrp has a dual recognition pattern in B. subtilis, i.e., for the canonical tryptophan codon and for readthrough at the UGA stop codon. ..
  43. Takeshima Y, Yagi M, Okizuka Y, Awano H, Zhang Z, Yamauchi Y, et al. Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J Hum Genet. 2010;55:379-88 pubmed publisher
    ..At one Japanese referral center, the hospital-based mutation database of the dystrophin gene was for the first time established with the highest levels of quality and patient's number. ..
  44. Deng J, Szyf M. Multiple isoforms of DNA methyltransferase are encoded by the vertebrate cytosine DNA methyltransferase gene. J Biol Chem. 1998;273:22869-72 pubmed
    ..The data presented here point toward a new mechanism for generating diversity of DNA MeTases and possibly diverse DNA methylation patterns. ..
  45. Nishimoto M, Fukushima A, Miyagi S, Suzuki Y, Sugano S, Matsuda Y, et al. Structural analyses of the UTF1 gene encoding a transcriptional coactivator expressed in pluripotent embryonic stem cells. Biochem Biophys Res Commun. 2001;285:945-53 pubmed
    ..Chromosomal mapping analyses locate the gene at 7F5, the syntenic region of the human chromosome (10q26) where the human UTF1 gene is located. ..
  46. Han Y, Zhu Y. [Human hR24L gene is involved in DNA excision repair and recombination repair]. Zhonghua Yi Xue Za Zhi. 1999;79:941-3 pubmed
    ..Human DNA repair gene hR24L was successfully cloned in this study. The product hR24L is involved in both DNA excision repair and recombination repair. ..
  47. Charest A, Lane K, McMahon K, Park J, Preisinger E, Conroy H, et al. Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21). Genes Chromosomes Cancer. 2003;37:58-71 pubmed
    ..This is the first example of a fusion RTK protein that results from an intra-chromosomal deletion, and it represents the first fusion RTK protein isolated from a human astrocytoma. ..
  48. Dominguez Martinez V, Guarneros Peña G, Segura Nieto M, Curiel Quesada E. Construction of a multiframe vector to express coding sequences in Escherichia coli. Can J Microbiol. 2001;47:72-6 pubmed
    ..To test the feasibility of this proposal, we cloned DNA fragments of the lacZ gene in each of the possible reading frames downstream from pMFV7 start codons...
  49. Segues B, Veber P, Rabier D, Calvas P, Saudubray J, Gilbert Dussardier B, et al. A 3-base pair in-frame deletion in exon 8 (delGlu272/273) of the ornithine transcarbamylase gene in late-onset hyperammonemic coma. Hum Mutat. 1996;8:373-4 pubmed
  50. Thanbichler M, Neuhierl B, Bock A. S-methylmethionine metabolism in Escherichia coli. J Bacteriol. 1999;181:662-5 pubmed
    ..The physiological roles of the ykfD and yagD products appear to reside in the acquisition of S-methylmethionine, which is an abundant plant product, and its utilization for methionine biosynthesis. ..
  51. Matsuo M, Takeshima Y. [Mutation-specific treatments for Duchenne muscular dystrophy]. Brain Nerve. 2009;61:915-22 pubmed
    ..The treatment with PTC124 is currently under clinical trial. In this review, these treatments strategies have been summarized. ..
  52. Walewski J, Gutierrez J, Branch Elliman W, Stump D, Keller T, Rodriguez A, et al. Mutation Master: profiles of substitutions in hepatitis C virus RNA of the core, alternate reading frame, and NS2 coding regions. RNA. 2002;8:557-71 pubmed
    ..This study is the first application of Mutation Master, which is now available upon request ( ..
  53. Phelps S, Gaudin C, Yoshizawa S, Benitez C, Fourmy D, Joseph S. Translocation of a tRNA with an extended anticodon through the ribosome. J Mol Biol. 2006;360:610-22 pubmed
    ..Flexibility within the loop may allow conformational adjustment upon A site binding and for interacting with the four nucleotide codon in order to shift the mRNA reading frame. ..