Michael Howard, Ph.D.

The rules of the genetic code were originally thought to be immutable, 20 standard amino acids were encoded by triplet nucleotides called codons, one codon specified initiation of translation and three codons specified termination. As in all aspects of biology there are exceptions and it became clear by the 1980s that other layers of information had evolved in specific messenger RNAs that could direct non-standard genetic decoding to modulate protein expression. 

This phenomenon is broadly referred to as recoding, which includes non-triplet decoding (ribosome frameshifting), stop codon decoding as a standard amino acid (readthrough), and perhaps the most surprising, redefinition of UGA codons to encode the 21st amino acid selenocysteine. The fascinating mechanisms that direct and regulate translational recoding are the subject of study in my laboratory.

Copeland PR, Howard MT. Ribosome Fate during Decoding of UGA-Sec Codons. Int J Mol Sci. 2021 Dec 8;22(24). doi: 10.3390/ijms222413204. Review. PubMed PMID: 34948001; PubMed Central PMCID: PMC8704476. 

Zhao W, Bohleber S, Schmidt H, Seeher S, Howard MT, Braun D, Arndt S, Reuter U, Wende H, Birchmeier C, Fradejas-Villar N, Schweizer U. Ribosome profiling of selenoproteins in vivo reveals consequences of pathogenic Secisbp2 missense mutations. J Biol Chem. 2019 Jul 26. pii: jbc.RA119.009369. doi:

10.1074/jbc.RA119.009369. [Epub ahead of print] PubMed PMID: 31350336.

Howard MT, Copeland PR. New Directions for Understanding the Codon Redefinition Required for Selenocysteine Incorporation. Biol Trace Elem Res. 2019 Jul 24. doi: 10.1007/s12011-019-01827-y. [Epub ahead of print] PubMed PMID: 31342342.

Mariotti M, Shetty S, Baird L, Wu S, Loughran G, Copeland PR, Atkins JF, Howard MT. Multiple RNA structures affect translation initiation and UGA redefinition efficiency during synthesis of selenoprotein P. Nucleic Acids Res. 2017 Dec 15;45(22):13004-13015. doi: 10.1093/nar/gkx982. PubMed PMID: 29069514; PubMed Central PMCID: PMC5727441.

Dalley BK, Baird L, Howard MT. Studying Selenoprotein mRNA Translation Using RNA-Seq and Ribosome Profiling. Methods Mol Biol. 2018;1661:103-123. doi: 10.1007/978-1-4939-7258-6_8. PubMed PMID: 28917040.

Drummond MJ, Reidy PT, Baird LM, Dalley BK, Howard MT. Leucine Differentially Regulates Gene-Specific Translation in Mouse Skeletal Muscle. J Nutr. 2017 Sep;147(9):1616-1623. doi: 10.3945/jn.117.251181. Epub 2017 Jun 14. PubMed PMID: 28615380; PubMed Central PMCID: PMC5572492.

Loughran G, Howard MT, Firth AE, Atkins JF. Avoidance of reporter assay distortions from fused dual reporters. RNA. 2017 Aug;23(8):1285-1289. doi: 10.1261/rna.061051.117. Epub 2017 Apr 25. PubMed PMID: 28442579; PubMed Central PMCID: PMC5513072.

Fradejas-Villar N, Seeher S, Anderson CB, Doengi M, Carlson BA, Hatfield DL, Schweizer U, Howard MT. The RNA-binding protein Secisbp2 differentially modulates UGA codon reassignment and RNA decay. Nucleic Acids Res. 2017 Apr 20;45(7):4094-4107. doi: 10.1093/nar/gkw1255. PubMed PMID: 27956496; PubMed Central PMCID: PMC5397149.

Wein N, Vulin A, Falzarano MS, Szigyarto CA, Maiti B, Findlay A, Heller KN, Uhlén M, Bakthavachalu B, Messina S, Vita G, Passarelli C, Brioschi S, Bovolenta M, Neri M, Gualandi F, Wilton SD, Rodino-Klapac LR, Yang L, Dunn DM, Schoenberg DR, Weiss RB, Howard MT, Ferlini A, Flanigan KM. Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. Nat Med. 2014 Sep;20(9):992-1000. doi: 10.1038/nm.3628. Epub 2014 Aug 10. Erratum in: Nat Med. 2015 Apr;21(4):414. Nat Med. 2015 May;21(5):537. PubMed PMID: 25108525; PubMed Central PMCID: PMC4165597.

Howard MT, Carlson BA, Anderson CB, Hatfield DL. Translational redefinition of UGA codons is regulated by selenium availability. J Biol Chem. 2013 Jul 5;288(27):19401-13. doi: 10.1074/jbc.M113.481051. Epub 2013 May 21. PubMed PMID:  23696641; PubMed Central PMCID: PMC3707644.

Fixsen SM, Howard MT. Processive selenocysteine incorporation during synthesis of eukaryotic selenoproteins. J Mol Biol. 2010 Jun 11;399(3):385-96. doi: 10.1016/j.jmb.2010.04.033. Epub 2010 Apr 24. PubMed PMID: 20417644; PubMed Central PMCID: PMC2916059.