Retron
Description
Retrons are distinct genetic elements found in bacterial genomes that code for a reverse transcriptase (RT) and a non-coding RNA (ncRNA). These elements generate a unique satellite DNA/RNA hybrid in the cell termed multicopy single-stranded DNA (msDNA). Retrons were recently found to function as anti-phage defense systems protecting bacteria against phage infection (N/A) . Their defensive unit is composed of three components: the reverse transcriptase, the non-coding RNA, and an effector protein.
Discovery
Discovery Retrons were originally discovered in 1984 in Myxococcus xanthus, when Yee et al. (N/A) identified a high copy, short, single-stranded linear ex-chromosomal DNA fragment in the gram-negative bacterium, Myxococcus xanthus. These multi-copy single-stranded DNA fragments were termed msDNA. Further studies showed that this single-stranded DNA (ssDNA) is covalently linked to an RNA molecule (N/A) . Although at the time reverse transcriptases were only known from Eukaryotes and viruses, Inouye and colleagues hypothesized that msDNA must be a product of a reverse transcription reaction (N/A) . Five years later an RT was shown to be associated with the biosynthesis of msDNA (N/A, N/A) , this was the first discovery of an RT in bacteria.
Although retrons were biochemically well studied and characterized, it was only 36 years after msDNA discovery, that their biological function was discovered (N/A) . In a systematic screen for the discovery of novel anti-phage defense systems in bacterial genomes (N/A) , Millman et al. discovered a new defense system that contained a retron element (Retron-Eco8), further analysis showed that retrons are enriched in bacterial defense islands and together with their accessory proteins many were shown to confer defense against phage infection (N/A) . An independent screen for defense systems, later that same year, also reported similar conclusions showing retrons function in antiphage defense (N/A) .
Due to their ability to produce a high copy of DNA within the cell, since their discovery retrons have served as a fertile ground for biotechnological applications (N/A, N/A, N/A)
Molecular mechanisms
General
When the retron ncRNA (msr-msd) is transcribed it folds into a typical structure that is recognized by the RT (N/A) . The RT then reverse transcribes a portion of the ncRNA (msd), starting from the 2′-end of a conserved guanosine residue found immediately after a double-stranded RNA structure within the ncRNA (N/A) . During reverse transcription, cellular RNase H degrades the segment of the ncRNA that serves as a template, but not other parts of the ncRNA (msr), yielding the mature RNA-DNA hybrid (msDNA) (N/A) . In some cases cellular nucleases have been shown to further process the msDNA (N/A, N/A, N/A) .
Retron-Eco6 (Ec48)
The Retron-Eco6 system encodes in addition to the retron an effector protein containing 2 transmembrane domains (2TM). Retron-Eco6 was shown to protect bacteria against phage through abortive infection (Abi) by guarding the integrity of the RecBCD complex in the cell. Many phages inhibit RecBCD to successfully infect the cell. Upon inhibition of RecBCD, the effector protein turns the membrane permeable and the cells lyse within 45 minutes post infection (N/A) .
Retron-Sen2 (St85), Retron-Eco9
The Retron-Sen2 system was shown to function as a three-partite toxin-antitoxin (TA) system. The accessory gene RcaT acts as a bona fide toxin and ectopically inhibits growth. The Retron-RT-msDNA complex acts as an antitoxin alleviating RcaT toxicity. Several triggers were identified for the Sen2-TA system, including Dam that was shown to methylate the mature msDNA and thus likely disrupt the RcaT–RT–msDNA complex, and RecE that degrades mature msDNA and reduces the RT-msDNA antitoxin levels (N/A)
Example of genomic structure
A total of 16 subsystems have been described for the Retron system.
Here are some examples found in the RefSeq database:
The Retron_II system in Agrobacterium tumefaciens (GCF_017726655.1, NZ_CP072309) is composed of 2 proteins NDT (WP_209089758.1) RT_Tot (WP_209089760.1)
The Retron_III system in Dokdonia sp. 4H-3-7-5 (GCF_000212355.1, NC_015496) is composed of 3 proteins PRTase (WP_148236012.1) WH (WP_013752369.1) RT_Tot (WP_013752370.1)
The Retron_IV system in Pseudomonas lurida (GCF_001708485.1, NZ_CP015639) is composed of 2 proteins RT_Tot (WP_081327059.1) 2TM (WP_145980332.1)
The Retron_I_A system in Hafnia alvei (GCF_902387815.1, NZ_LR699008) is composed of 3 proteins RT_Tot (WP_197737714.1) ATPase_TypeIA (WP_111329110.1) HNH_TIGR02646 (WP_111329111.1)
The Retron_I_B system in Dickeya zeae (GCF_012278555.1, NZ_CP033622) is composed of 2 proteins ATPase_TOPRIM_COG3593 (WP_168363308.1) RT_Tot (WP_168363309.1)
The Retron_I_C system in Proteus vulgaris (GCF_009931275.1, NZ_CP034668) is composed of 1 protein: RT_1_C1 (WP_017628371.1)
The Retron_VI system in Enterobacter roggenkampii (GCF_013728935.1, NZ_CP056148) is composed of 2 proteins HTH (WP_008499884.1) RT_Tot (WP_016243639.1)
The Retron_VII_1 system in Hypericibacter terrae (GCF_008728855.1, NZ_CP042906) is composed of 1 protein: RT_7_A1 (WP_151178207.1)
The Retron_VII_2 system in Sideroxydans lithotrophicus (GCF_000025705.1, NC_013959) is composed of 2 proteins RT_Tot (WP_013028226.1) DUF3800 (WP_013028227.1)
The Retron_XI system in Sphingopyxis granuli (GCF_022637755.1, NZ_CP093335) is composed of 1 protein: RT_11 (WP_241940850.1)
The Retron_XII system in Tenuifilum thalassicum (GCF_013265555.1, NZ_CP041345) is composed of 1 protein: RT_12 (WP_173072943.1)
The Retron_XIII system in Clostridium saccharobutylicum (GCF_002003365.1, NZ_CP016091) is composed of 3 proteins ARM (WP_022745963.1) WHSWIM (WP_022745966.1) RT_Tot (WP_022745969.1)
Distribution of the system among prokaryotes
Structure
Group | Structure | Foldseek | System | Gene name | Subtype | Proteins in structure | System genes | Prediction type | N genes in sys | pLDDT | iptm+ptm | pDockQ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No data available | ||||||||||||