Bacterial retrons function in anti-phage defense

Millman, Adi; Bernheim, Aude; Stokar-Avihail, Avigail; Fedorenko, Taya; Voichek, Maya; Leavitt, Azita; Sorek, Rotem

doi:10.1101/2020.06.21.156273

Cited by 47 publications

(72 citation statements)

References 59 publications

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“…The first of these roles is thought to be mediated by the RT and msDNA, with the linked effector protein responsible for toxin/antitoxin functions. Furthermore, according to these reports ( 81 , 82 ), a large number of retrons, but not all are associated with defense genes in defense islands. It would be interesting to know whether there are specific retron systems consistently unrelated the known and novel candidate defense systems recently described ( 81 ).…”

Section: Discussionmentioning

confidence: 98%

“…Recently, it was reported that some retrons members of the type systems I-A (Retron+ATPase+HNH), II-A3 (Nuc_deoxy+Retron), I-C1 (Retron-Toprim) and XII (Retron-TIR) defined here mediate antiphage defense and that the additional proteins or RT-fused domains are also required for activity ( 81 ). Moreover, a recent report ( 82 ) and two pre-prints ( 83 , 84 ) have also suggested that retrons may be novel anti-phage defense systems and that they may function as a toxin/antitoxin system. The first of these roles is thought to be mediated by the RT and msDNA, with the linked effector protein responsible for toxin/antitoxin functions.…”

Section: Discussionmentioning

confidence: 99%

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Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems

Mestre

González-Delgado

Gutierrez-Rus

et al. 2020

Nucleic Acids Research

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Bacterial retrons consist of a reverse transcriptase (RT) and a contiguous non-coding RNA (ncRNA) gene. One third of annotated retrons carry additional open reading frames (ORFs), the contribution and significance of which in retron biology remains to be determined. In this study we developed a computational pipeline for the systematic prediction of genes specifically associated with retron RTs based on a previously reported large dataset representative of the diversity of prokaryotic RTs. We found that retrons generally comprise a tripartite system composed of the ncRNA, the RT and an additional protein or RT-fused domain with diverse enzymatic functions. These retron systems are highly modular, and their components have coevolved to different extents. Based on the additional module, we classified retrons into 13 types, some of which include additional variants. Our findings provide a basis for future studies on the biological function of retrons and for expanding their biotechnological applications.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems

Mestre

González-Delgado

Gutierrez-Rus

et al. 2020

Nucleic Acids Research

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“…Recent booming of metagenomic analysis has suggested that a large number of uncharacterized defense systems exist in bacteria (9). As predicted, an increasing number of defense system were validated successively (10)(11)(12). Doron et al predicted and experimentally verified ten potential anti-phage defense systems, although their molecular mechanisms are not yet understood (10).…”

Section: Introductionmentioning

confidence: 97%

A nucleotide-sensing endonuclease from the Gabija bacterial defense system

Cheng

Huang

et al. 2020

Preprint

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The arms race between bacteria and phages has led to the development of exquisite bacterial defense systems including a number of uncharacterized systems distinct from the well-known Restriction-Modification and CRISPR/Cas systems. Here, we report functional analyses of the GajA protein from the newly predicted Gabija system. The GajA protein is revealed as an endonuclease unique in that: 1. It may function as a restriction enzyme or a site-specific nicking enzyme, depending on the arrangement of the recognition sequences; 2. Its activity is strictly regulated by nucleotides concentration. NTP and dNTP at physiological concentrations can fully inhibited the robust DNA cleavage activity of GajA. Interestingly, the nucleotide inhibition is mediated by an ATPase-like domain, which usually hydrolyzes ATP to stimulate the DNA cleavage when associated with other nucleases. These features suggested the mechanism of the Gabija defense in which an endonuclease activity was suppressed at normal condition, while activated by the depletion of NTP and dNTP upon the replication and transcription by invaded phages. This work highlights a concise strategy to utilize a single protein for phage resistance via nucleotide regulatory.

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“…Retrons encode 12%-14% of the bacterial RTs and are the second frequent class of RTs [4,6]. Although retrons were discovered three decades ago, their function remained unknown until recently that they were found to function as phage defense mechanisms [11,12]. Bacterial retrons are non-LTR-retroelements that produce multicopy single-stranded DNAs (msDNAs).…”

Section: Introductionmentioning

confidence: 99%

Identification and Classification of Reverse Transcriptases in Bacterial Genomes and Metagenomes

Sharifi

2021

Preprint

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Reverse Transcriptases (RTs) are found in different systems including group II introns, Diversity Generating Retroelements (DGRs), retrons, CRISPR-Cas systems, and Abortive Infection (Abi) systems in prokaryotes. Different classes of RTs can play different roles, such as template switching and mobility in group II introns, spacer acquisition in CRISPR-Cas systems, mutagenic retrohoming in DGRs, programmed cell suicide in Abi systems, and recently discovered phage defense in retrons. While some classes of RTs have been studied extensively, others remain to be characterized. There is a lack of computational tools for identifying and characterizing various classes of RTs. In this study, we built a tool (called myRT) for identification and classification of prokaryotic RTs. In addition, our tool provides information about the genomic neighborhood of each RT, providing potential functional clues. We applied our tool to predict and classify RTs in all complete and draft bacterial genomes, and created a collection that can be used for exploration of putative RTs. Application of myRT to gut metagenomes showed that gut metagenomes encode proportionally more RTs related to DGRs, outnumbering retron-related RTs, as compared to the collection of reference genomes. MyRT is both available as a standalone software and also through a website.

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Bacterial retrons function in anti-phage defense

Cited by 47 publications

References 59 publications

Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems

Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems

A nucleotide-sensing endonuclease from the Gabija bacterial defense system

Identification and Classification of Reverse Transcriptases in Bacterial Genomes and Metagenomes

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