Biography
John went from Dunmanway Co. Cork to obtain his degrees from the Department of Genetics in Trinity College Dublin (where he is an Honorary Professor). He is engaged in doing research full time though there have been brief periods when he also lectured (in UCC's Biochem. Dept.) or was also an administrator (the first Director for Life Sciences in Science Foundation Ireland). Apart from the excitement of the dramatic technical and conceptual advances in molecular biology, John gets pleasure from interacting with some great outside collaborators and UCC lab members several of whom are benefiting from his ongoing work in the Department of Human Genetics in the University of Utah. Our lab in UCC is part of the BioSciences Institute and John is a member of both the Biochemistry and Microbiology Departments. Other memberships include EMBO, RIA and the RNA Society.Research Interests
Genetic decoding is dynamic. It can be altered in an mRNA- or site-specific manner and in a remarkable variety of ways. The meaning of individual codons can be redefined in response to signals in mRNA. A proportion of translating ribosomes can be diverted at a specific site to a different reading frame. They can also be directed to bypass a block of nucleotides - at least up to 50 - or even to resume on a different mRNA. We are studying these "recoding" phenomena to determine where they occur, understand their functional significance, elucidate the mechanisms involved, and where desirable plot intervention strategies.
Recoding is used for a subset of mRNAs in probably all organisms with some types being most prevalent in the decoding of viral genomes and mobile elements. In some cases it is exploited for regulatory purposes. In others it yields an extra product with distinctive functions at a set ratio to the product of standard decoding (as in HIV decoding). One class of codon redefinition involves UGA specifying the 21st encoded amino acid, selenocysteine rather than termination (our studies of this aspect are focused on the mammalian selenoprotein P mRNA coding sequence where there are 10 UGA codons, all of them specifying selenocysteine).
A variety of recoding signals are used to reprogram the ribosomes. Some are mRNA signals 5' of the recoding site, others are specific nascent peptide signals encoded 5' of the recoding site, that interact with the ribosome peptide exit tunnel to cause conformational alterations. Yet others are 3' of the recoding site - and only some of these are a variety of specific intra-mRNA structure. Synthetic trans-acting small RNAs can mimic the effect of certain recoding signals to ameliorate mutant phenotypes, but whether any natural small RNAs act in trans as recoding signals is unknown but ripe for investigation. With increasing structural knowledge of ribosome conformational changes, the prospect of at last understanding how ribosomes sense and respond to recoding signals is approaching.
The most immediately exciting prospects are being able to systematically find where recoding is utilized. The deluge of DNA sequence information and its analysis is facilitating this. However, a recently developed technique that permits identification of the location and framing of all ribosomes promises to be a bonanza and allow the realization of a dream that for a long time seemed distant. In a broader perspective we interested in the multiple unrecognized types of RNA with diverse roles in gene expression that are being discovered and characterized. The implications of the roles of some RNAs in present day organisms for hypotheses of the origin of protein synthesis and an ancient RNA World are fascinating.
Publications
Books
| Year | Publication | |
|---|---|---|
| (2019) | RNA Worlds: New Tools for Deep Exploration. Thomas R. Cech, Joan A. Steitz, and John F. Atkins (2019) RNA Worlds: New Tools for Deep Exploration. Cold Spring Harbor, New York, United States: Cold Spring Harbor Laboratory Press. [Details] |
Peer Reviewed Journals
| Year | Publication | |
|---|---|---|
| (2022) | 'Maximum depth sequencing reveals an ON/OFF replication slippage switch and apparent in vivo selection for bifidobacterial pilus expression' Penno C; Motherway MO; Fu Y; Sharma V; Crispie F; Cotter PD; Houeix B; Joshi L; Bottacini F; O'Dwyer A; Loughran G; Atkins JF; van Sinderen D; (2022) 'Maximum depth sequencing reveals an ON/OFF replication slippage switch and apparent in vivo selection for bifidobacterial pilus expression'. Scientific Reports, 12 (1) [DOI] [Details] | |
| (2022) | 'Stop codon readthrough contexts influence reporter expression differentially depending on the presence of an IRES' Yordanova MM;Loughran G;Atkins JF;Baranov PV; (2022) 'Stop codon readthrough contexts influence reporter expression differentially depending on the presence of an IRES'. Wellcome Open Research, 5 [DOI] [Details] | |
| (2021) | 'Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome' Bhatt, PR;Scaiola, A;Loughran, G;Leibundgut, M;Kratzel, A;Meurs, R;Dreos, R;O'Connor, KM;McMillan, A;Bode, JW;Thiel, V;Gatfield, D;Atkins, JF;Ban, NN (2021) 'Structural basis of ribosomal frameshifting during translation of the SARS-CoV-2 RNA genome'. Science, 372 [DOI] [Details] | |
| (2021) | 'Tissue-specific dynamic codon redefinition in Drosophila' Hudson, AM;Loughran, G;Szabo, NL;Wills, NM;Atkins, JF;Cooley, L (2021) 'Tissue-specific dynamic codon redefinition in Drosophila'. Proceedings of The National Academy of Sciences of The United States of America, 118 [DOI] [Details] | |
| (2020) | 'Unusually efficient CUG initiation of an overlapping reading frame in POLG mRNA yields novel protein POLGARF' Loughran, G;Zhdanov, AV;Mikhaylova, MS;Rozov, FN;Datskevich, PN;Kovalchuk, SI;Serebryakova, MV;Kiniry, SJ;Michel, AM;O'Connor, PBF;Papkovsky, DB;Atkins, JF;Baranov, PV;Shatsky, IN;Andreev, DE (2020) 'Unusually efficient CUG initiation of an overlapping reading frame in POLG mRNA yields novel protein POLGARF'. Proceedings of The National Academy of Sciences of The United States of America, 117 :24936-24946 [DOI] [Details] | |
| (2020) | 'Polysomes Bypass a 50-Nucleotide Coding Gap Less Efficiently Than Monosomes Due to Attenuation of a 5' mRNA Stem–Loop and Enhanced Drop-off' O'Loughlin S.;Capece M.C.;Klimova M.;Wills N.M.;Coakley A.;Samatova E.;O'Connor P.B.F.;Loughran G.;Weissman J.S.;Baranov P.V.;Rodnina M.V.;Puglisi J.D.;Atkins J.F. (2020) 'Polysomes Bypass a 50-Nucleotide Coding Gap Less Efficiently Than Monosomes Due to Attenuation of a 5' mRNA Stem–Loop and Enhanced Drop-off'. Journal of Molecular Biology, [DOI] [Details] | |
| (2020) | 'The energy landscape of -1 ribosomal frameshifting' Choi J.;O’Loughlin S.;Atkins J.;Puglisi J. (2020) 'The energy landscape of -1 ribosomal frameshifting'. Science Advances, 6 (1) [DOI] [Details] | |
| (2019) | 'Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs' Baclaocos J;Santesmasses D;Mariotti M;Bierla K;Vetick MB;Lynch S;McAllen R;Mackrill JJ;Loughran G;Guigó R;Szpunar J;Copeland PR;Gladyshev VN;Atkins JF; (2019) 'Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs'. Journal of Molecular Biology, [DOI] [Details] | |
| (2018) | 'Stop codon readthrough generates a C-terminally extended variant of the human vitamin D receptor with reduced calcitriol response' Loughran, Gary; Jungreis, Irwin; Tzani, Ioanna; Power, Michael; Dmitriev, Ruslan I.; Ivanov, Ivaylo P.; Kellis, Manolis; Atkins, John F. (2018) 'Stop codon readthrough generates a C-terminally extended variant of the human vitamin D receptor with reduced calcitriol response'. Journal of Biological Chemistry, 293 (12):4434-4444 [DOI] [Full Text] [Details] | |
| (2018) | 'Translational autoregulation of BZW1 and BZW2 expression by modulating the stringency of start codon selection' Loughran, G;Firth, AE;Atkins, JF;Ivanov, IP (2018) 'Translational autoregulation of BZW1 and BZW2 expression by modulating the stringency of start codon selection'. Plos One, 13 [DOI] [Details] | |
| (2018) | 'Polyamine Control of Translation Elongation Regulates Start Site Selection on Antizyme Inhibitor mRNA via Ribosome Queuing' Ivanov, IP;Shin, BS;Loughran, G;Tzani, I;Young-Baird, SK;Cao, C;Atkins, JF;Dever, TE (2018) 'Polyamine Control of Translation Elongation Regulates Start Site Selection on Antizyme Inhibitor mRNA via Ribosome Queuing'. Molecular Cell, 70 [DOI] [Details] | |
| (2018) | 'AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation' Yordanova, Martina M.; Loughran, Gary; Zhdanov, Alexander V.; Mariotti, Marco; Kiniry, Stephen J.; O’Connor, Patrick B. F.; Andreev, Dmitry E.; Tzani, Ioanna; Saffert, Paul; Michel, Audrey M.; Gladyshev, Vadim N.; Papkovsky, Dmitry B.; Atkins, John F.; Baranov, Pavel V. (2018) 'AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation'. Nature, 553 :356-360 [DOI] [Full Text] [Details] | |
| (2017) | 'Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P' Mariotti, M;Shetty, S;Baird, L;Wu, S;Loughran, G;Copeland, PR;Atkins, JF;Howard, MT (2017) 'Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P'. Nucleic acids research, 45 [DOI] [Details] | |
| (2017) | 'ASXL gain-of-function truncation mutants: defective and dysregulated forms of a natural ribosomal frameshifting product?' Dinan, AM;Atkins, JF;Firth, AE (2017) 'ASXL gain-of-function truncation mutants: defective and dysregulated forms of a natural ribosomal frameshifting product?'. Biology Direct, 12 [DOI] [Details] | |
| (2017) | 'Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis' Penno, C;Kumari, R;Baranov, PV;van Sinderen, D;Atkins, JF (2017) 'Specific reverse transcriptase slippage at the HIV ribosomal frameshift sequence: potential implications for modulation of GagPol synthesis'. Nucleic acids research, 45 :10156-10167 [DOI] [Details] | |
| (2017) | 'Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity' Ivanov, IP;Wei, JJ;Caster, SZ;Smith, KM;Michel, AM;Zhang, Y;Firth, AE;Freitag, M;Dunlap, JC;Bell-Pedersen, D;Atkins, JF;Sachs, MS (2017) 'Translation Initiation from Conserved Non-AUG Codons Provides Additional Layers of Regulation and Coding Capacity'. Mbio, 8 [DOI] [Details] | |
| (2017) | 'Stimulation of reverse transcriptase generated cDNAs with specific indels by template RNA structure: retrotransposon, dNTP balance, RT-reagent usage' Penno, C;Kumari, R;Baranov, PV;van Sinderen, D;Atkins, JF (2017) 'Stimulation of reverse transcriptase generated cDNAs with specific indels by template RNA structure: retrotransposon, dNTP balance, RT-reagent usage'. Nucleic acids research, 45 :10143-10155 [DOI] [Details] | |
| (2017) | 'Avoidance of reporter assay distortions from fused dual reporters' Loughran, G;Howard, MT;Firth, AE;Atkins, JF (2017) 'Avoidance of reporter assay distortions from fused dual reporters'. Rna-A Publication of The Rna Society, 23 :1285-1289 [DOI] [Details] | |
| (2017) | 'Position-dependent termination and widespread obligatory frameshifting in Euplotes translation' Lobanov, AV;Heaphy, SM;Turanov, AA;Gerashchenko, MV;Pucciarelli, S;Devaraj, RR;Xie, F;Petyuk, VA;Smith, RD;Klobutcher, LA;Atkins, JF;Miceli, C;Hatfield, DL;Baranov, PV;Gladyshev, VN (2017) 'Position-dependent termination and widespread obligatory frameshifting in Euplotes translation'. Nature Structural &Amp; Molecular Biology, 24 :61-68 [DOI] [Details] | |
| (2016) | 'Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements' Wu, S;Mariotti, M;Santesmasses, D;Hill, KE;Baclaocos, J;Aparicio-Prat, E;Li, SP;Mackrill, J;Wu, YY;Howard, MT;Capecchi, M;Guigo, R;Burk, RF;Atkins, JF (2016) 'Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements'. Open Biology, 6 [DOI] [Details] | |
| (2016) | 'Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop Codons to Sense Codons in Condylostoma magnum' Heaphy, SM;Mariotti, M;Gladyshev, VN;Atkins, JF;Baranov, PV (2016) 'Novel Ciliate Genetic Code Variants Including the Reassignment of All Three Stop Codons to Sense Codons in Condylostoma magnum'. Molecular biology and evolution, 33 :2885-2889 [DOI] [Details] | |
| (2016) | 'An Expanded CAG Repeat in Huntingtin Causes+1 Frameshifting' Saffert, P; Adamla, F;Schieweck, R;Atkins, JF; Ignatova, Z (2016) 'An Expanded CAG Repeat in Huntingtin Causes+1 Frameshifting'. The Journal of Biological Chemistry, 291 :18505-18513 [DOI] [Details] | |
| (2016) | 'Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use' Atkins, JF,Loughran, G,Bhatt, PR,Firth, AE,Baranov, PV (2016) 'Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use'. Nucleic acids research, 44 :7007-7078 [DOI] [Details] | |
| (2016) | 'Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform' Tzani I;Ivanov IP;Andreev DE;Dmitriev RI;Dean KA;Baranov PV;Atkins JF;Loughran G; (2016) 'Systematic analysis of the PTEN 5' leader identifies a major AUU initiated proteoform'. Open Biology, 6 (5) [DOI] [Details] | |
| (2015) | 'Coupling of mRNA Structure Rearrangement to Ribosome Movement during Bypassing of Non-coding Regions' Chen, J,Coakley, A,O'Connor, M,Petrov, A,O'Leary, SE,Atkins, JF,Puglisi, JD (2015) 'Coupling of mRNA Structure Rearrangement to Ribosome Movement during Bypassing of Non-coding Regions'. Cell, 163 :1267-1280 [DOI] [Details] | |
| (2015) | 'Transcriptional slippage in the positive-sense RNA virus family Potyviridae' Olspert, A; Chung, BYW; Atkins, JF; Carr, JP; Firth, AE (2015) 'Transcriptional slippage in the positive-sense RNA virus family Potyviridae'. Embo Reports, 16 :995-1004 [Details] | |
| (2015) | 'Productive mRNA stem loop-mediated transcriptional slippage: Crucial features in common with intrinsic terminators' Penno, C; Sharma, V; Coakley, A; Motherway, MO; van Sinderen, D; Lubkowska, L; Kireeva, ML; Kashlev, M; Baranov, PV; Atkins, JF (2015) 'Productive mRNA stem loop-mediated transcriptional slippage: Crucial features in common with intrinsic terminators'. Proceedings of The National Academy of Sciences of The United States of America, 112 :1984-1993 [DOI] [Details] | |
| (2015) | 'A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA' Yordanova, Martina M.; Wu, Cheng; Andreev, Dmitry E.; Sachs, Matthew S.; Atkins, John F. (2015) 'A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA'. The Journal of Biological Chemistry, 290 (29):17863-17878 [DOI] [Full Text] [Details] |
Articles
| Year | Publication | |
|---|---|---|
| (2022) | Immune cells alter genetic decoding in cancer. Baranov PV; Atkins JF; (2022) Immune cells alter genetic decoding in cancer. London, UK: Articles [DOI] [Details] |
Editorship
| Year | Publication | |
|---|---|---|
| (2018) | Culmination of a half-century quest reveals insight into mutant tRNA-mediated frameshifting after tRNA departure from the decoding site. Atkins, JF (2018) Culmination of a half-century quest reveals insight into mutant tRNA-mediated frameshifting after tRNA departure from the decoding site. WASHINGTON: Editorship [DOI] [Details] | |
| (2017) | A [Cu]rious Ribosomal Profiling Pattern Leads to the Discovery of Ribosomal Frameshifting in the Synthesis of a Copper Chaperone. Atkins, JF;Loughran, G;Baranov, PV (2017) A [Cu]rious Ribosomal Profiling Pattern Leads to the Discovery of Ribosomal Frameshifting in the Synthesis of a Copper Chaperone. CAMBRIDGE: Editorship [Details] |
Published Letters
| Year | Publication | |
|---|---|---|
| (2022) | Evaluating ribosomal frameshifting in CCR5 mRNA decoding. Khan YA;Loughran G;Steckelberg AL;Brown K;Kiniry SJ;Stewart H;Baranov PV;Kieft JS;Firth AE;Atkins JF; (2022) Evaluating ribosomal frameshifting in CCR5 mRNA decoding. Published Letters [DOI] [Details] |
Reviews
| Year | Publication | |
|---|---|---|
| (2021) | From Recoding to Peptides for MHC Class I Immune Display: Enriching Viral Expression, Virus Vulnerability and Virus Evasion. Atkins, JF;O'Connor, KM;Bhatt, PR;Loughran, G (2021) From Recoding to Peptides for MHC Class I Immune Display: Enriching Viral Expression, Virus Vulnerability and Virus Evasion. BASEL: Reviews [DOI] [Details] | |
| (2018) | Pyrrolysine in archaea: a 22nd amino acid encoded through a genetic code expansion. Brugere, JF;Atkins, JF;O'Toole, PW;Borrel, G (2018) Pyrrolysine in archaea: a 22nd amino acid encoded through a genetic code expansion. LONDON: Reviews [DOI] [Details] | |
| (2015) | Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning. Baranov, PV;Atkins, JF;Yordanova, MM (2015) Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning. LONDON: Reviews [DOI] [Details] |
Professional Activities
Honours and Awards
| Year | Title | Awarding Body | |
|---|---|---|---|
| 2007 | Gold medal from the Royal Irish Academy (inaugural quadrennial medal in the Life Sciences) | Royal Irish Academy (inaugural quadrennial medal in the Life Sciences) |
Conference Contributions
| Year | Publication | |
|---|---|---|
| (2009) | NIH Symposium, Atkins, JF; (2009) Genes to Proteins: Decoding Genetic Information to honor Marshall Nirenberg almost 50 years after deciphering the genetic code. [Invited Oral Presentation], NIH Symposium, Bethesda , 12-NOV-09 - 12-NOV-09. [Details] |
Education
| Year | Institution | Qualification | Subject | |
|---|---|---|---|---|
| 1981 | Dublin University (TCD) | ScD |
Teaching Activities
Teaching Interests
John gave lectures for a few years in a Developmental Biology course for students of UCC's Microbiology and Biochemistry Departments and lectured in molecular biology to Biochemistry Dept. students.
The text of 195 pages with 4 experiments designed for school and college biology classes in association with the Biological Sciences Curriculum Study, in Colorado Springs by J.F. Atkins, A. Ellington, B.E. Friedman, R.F. Gesteland, H.F. Noller, S.M. Pasquale, R.D. Storey, O.C. Uhlenbeck and A.M. Weiner. 2000 entitled "Bringing RNA into view: RNA and its roles in biology" It was later placed on a web piece at the Learn Genetics website where it was downloaded over 26,000 times between 8/2002 -12/2003 (it was the most popular download on the site and 64,506 times between 7/05 and 5/08, but has now been transferred to http://learn.genetics.utah.edu/archive/rna/index.html as an update is being prepared (not involving JFA). The website won several awards including the first Science Prize for Online Resources in Education (SPORE) as described by B. Alberts, Editor-in Chief of Science, Science vol. 327, 504 (2010).