PXD041335

PXD041335 is an original dataset announced via ProteomeXchange.

Title	Mistranslation of the genetic code by a new family of bacterial transfer RNAs
Description	The correct coupling of amino acids with transfer RNAs (tRNAs) is vital for translating genetic information into functional proteins. Errors during this process lead to mistranslation, where a codon is translated using the wrong amino acid. While unregulated and prolonged mistranslation is often toxic, growing evidence suggests that organisms, from bacteria to humans, can induce and use mistranslation as a mechanism to overcome unfavorable environmental conditions. Most known cases of mistranslation are caused by translation factors with poor substrate specificity or when substrate discrimination is sensitive to molecular changes such as mutations or post-translational modifications. Here we report two novel families of tRNAs, encoded by bacteria from the Streptomyces and Kitasatospora genera, that adopted dual identities by integrating the anticodons AUU (for Asn) or AGU (for Thr) into the structure of a distinct proline tRNA. These tRNAs are typically encoded next to a full-length or truncated version of a distinct isoform of bacterial-type prolyl-tRNA synthetase. Using two protein reporters, we showed that these tRNAs translate asparagine and threonine codons with proline. Moreover, when expressed in Escherichia coli, the tRNAs cause varying growth defects due to global Asn-to-Pro and Thr-to-Pro mutations. Yet, proteome-wide substitutions of Asn with Pro induced by tRNA expression increased cell tolerance to the antibiotic carbenicillin, indicating that Pro mistranslation can be beneficial under certain conditions. Collectively, our results significantly expand the catalog of organisms known to possess dedicated mistranslation machinery and provide support for the concept that mistranslation is a mechanism for cellular resiliency against environmental stress.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:09:31.244.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041335
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kyle Hoffman
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-04 13:04:53	ID requested
1	2023-10-24 12:18:59	announced
⏵ 2	2023-11-14 09:09:37	announced	2023-11-14: Updated project metadata.

Schuntermann DB, Fischer JT, Bile J, Gaier SA, Shelley BA, Awawdeh A, Jahn M, Hoffman KS, Westhof E, S, ö, ll D, Clarke CR, Vargas-Rodriguez O, Mistranslation of the genetic code by a new family of bacterial transfer RNAs. J Biol Chem, 299(7):104852(2023) [pubmed]

10.6019/PXD041335;

submitter keyword: tRNA, aminoacyl-tRNA synthetase, Streptomyces, mistranslation, protein synthesis, genetic code, translation

Oscar Vargas-Rodriguez
contact affiliation	Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA
contact email	oscar.vargas@yale.edu
lab head
Kyle Hoffman
contact affiliation	Bioinformatics Solutions Inc.
contact email	khoffman@bioinfor.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041335
     1. Label: PRIDE project
     2. Name: Mistranslation of the genetic code by a new family of bacterial transfer RNAs