The sequences and activities of RegB endoribonucleases of T4-related bacteriophages

Piešiniene, Lina

doi:10.1093/nar/gkh892

Cited by 8 publications

(6 citation statements)

References 58 publications

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“…As in T4, the SD sequence of these regB genes is GGAG, with only one case (RB49) of GGAU. When experimentally tested, this sequence was always found to be cleaved by RegB in vivo , suggesting that translational auto-control of regB is conserved in T4-related phages [ 42 ].…”

Section: Posttranscriptional Control By Mrna Decaymentioning

confidence: 99%

Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation

Uzan

Miller

2010

Virol J

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Over 50 years of biological research with bacteriophage T4 includes notable discoveries in post-transcriptional control, including the genetic code, mRNA, and tRNA; the very foundations of molecular biology. In this review we compile the past 10 - 15 year literature on RNA-protein interactions with T4 and some of its related phages, with particular focus on advances in mRNA decay and processing, and on translational repression. Binding of T4 proteins RegB, RegA, gp32 and gp43 to their cognate target RNAs has been characterized. For several of these, further study is needed for an atomic-level perspective, where resolved structures of RNA-protein complexes are awaiting investigation. Other features of post-transcriptional control are also summarized. These include: RNA structure at translation initiation regions that either inhibit or promote translation initiation; programmed translational bypassing, where T4 orchestrates ribosome bypass of a 50 nucleotide mRNA sequence; phage exclusion systems that involve T4-mediated activation of a latent endoribonuclease (PrrC) and cofactor-assisted activation of EF-Tu proteolysis (Gol-Lit); and potentially important findings on ADP-ribosylation (by Alt and Mod enzymes) of ribosome-associated proteins that might broadly impact protein synthesis in the infected cell. Many of these problems can continue to be addressed with T4, whereas the growing database of T4-related phage genome sequences provides new resources and potentially new phage-host systems to extend the work into a broader biological, evolutionary context.

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Section: Posttranscriptional Control By Mrna Decaymentioning

confidence: 99%

Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation

Uzan

Miller

2010

Virol J

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“…As shown above, two GGAU sequences are efficiently cleaved by RegB in phage T4 (orf 55.2 and motB.2 ) and one was found in the T4-related phage, RB69 (11) (Figure 3A). Thus, a U in position 4 seems tolerated, but under strict conditions as the great majority of the intergenic GGAU sequences in T4 are resistant to RegB.…”

Section: Resultsmentioning

confidence: 60%

“…Many T4-related phages code for a homolog of the T4 RegB enzyme (11,38). The sequences of the few cleavage sites identified in four of these phages are shown in the middle part of Figure 3A.…”

Section: Resultsmentioning

confidence: 99%

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Activation of RegB endoribonuclease by S1 ribosomal protein requires an 11 nt conserved sequence

Durand¹,

Richard²,

Bisaglia

et al. 2006

Nucleic Acids Research

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The T4 RegB endoribonuclease cleaves specifically in the middle of the -GGAG- sequence, leading to inactivation and degradation of early phage mRNAs. In vitro, RegB activity is very weak but can be enhanced 10- to 100-fold by the Escherichia coli ribosomal protein S1. Not all RNAs carrying the GGAG motif are cleaved by RegB, suggesting that additional information is required to obtain a complete RegB target site. In this work, we find that in the presence of S1, the RegB target site is an 11 nt long single-stranded RNA carrying the 100% conserved GGA triplet at the 5′ end and a degenerate, A-rich, consensus sequence immediately downstream. Our data support the notion that RegB alone recognizes only the trinucleotide GGA, which it cleaves very inefficiently, and that stimulation of RegB activity by S1 depends on the nucleotide immediately 3′ to -GGA-.

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“…Interestingly, ribosomal protein S1 promotes the recognition of the translation initiation region by the ribosome when the Shine-Dalgarno sequence is degenerated (22). A regB gene has been identified in nearly all T4-like phages (23), but no related sequences could be identified in other organisms. This raises the question of the origin of RegB.…”

Section: Discussionmentioning

confidence: 99%

Structural and Functional Studies of RegB, a New Member of a Family of Sequence-specific Ribonucleases Involved in mRNA Inactivation on the Ribosome

Odaert

Saïda

Aliprandi

et al. 2007

Journal of Biological Chemistry

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The RegB endoribonuclease participates in the bacteriophage T4 life cycle by favoring early messenger RNA breakdown. RegB specifically cleaves GGAG sequences found in intergenic regions, mainly in translation initiation sites. Its activity is very low but can be enhanced up to 100-fold by the ribosomal 30 S subunit or by ribosomal protein S1. RegB has no significant sequence homology to any known protein. Here we used NMR to solve the structure of RegB and map its interactions with two RNA substrates. We also generated a collection of mutants affected in RegB function. Our results show that, despite the absence of any sequence homology, RegB has structural similarities with two Escherichia coli ribonucleases involved in mRNA inactivation on translating ribosomes: YoeB and RelE. Although these ribonucleases have different catalytic sites, we propose that RegB is a new member of the RelE/YoeB structural and functional family of ribonucleases specialized in mRNA inactivation within the ribosome.Control of messenger RNA decay is a key factor in the regulation of gene expression. Indeed, the expression level of a protein is strongly influenced by the concentration of its mRNA, which, in turn, depends on its synthesis and degradation rates (1). Perturbation of mRNA stability can lead to dramatic effects on cell physiology and in some cases can induce cancer (2). However, the way the cell controls the lifetime of its mRNA is still a poorly understood aspect in the biology of both prokaryotic and eukaryotic organisms. In Escherichia coli, it is generally agreed that the initiation of mRNA degradation is induced by an endoribonucleolytic cleavage mediated by ribonucleases E and G with the occasional involvement of RNases III and P (3, 4). These ribonucleases all generate 5Ј-phosphate RNA fragments (RNases E, G, and III are metallo-enzymes; RNase P is a ribozyme), have broad specificity, and are involved in other cellular functions. RNases E and G, for example, participate in the maturation of 9 S and 16 S rRNA (5), and RNase E is necessary for tRNA processing (6).Ribonuclease RegB is radically different from the ribonucleases described above. RegB is involved in the control of the bacteriophage T4 multiplication cycle. It is produced in the early stage of viral infection and facilitates the transition between the early and middle phases of the viral cycle by inactivating early mRNAs (7). RegB cleaves its substrates with high specificity in the middle of the GGAG motif found in the ribosome-binding site of most prokaryotic mRNAs (Shine-Dalgarno sequence). Strikingly, it remains active throughout the entire lytic cycle but does not act on middle or late mRNA (8). In contrast with RNases E, G, III, and P, RegB is only involved in this task and is certainly one of the most specific ribonucleases described to date. It only cleaves GGAG, or to a lesser extent and with reduced efficiency, GGAU sequences (7, 9). Moreover, it does not cleave all such sequences: those present in coding sequences and in middle or late T4 mRNAs are ...

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The sequences and activities of RegB endoribonucleases of T4-related bacteriophages

Cited by 8 publications

References 58 publications

Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation

Post-transcriptional control by bacteriophage T4: mRNA decay and inhibition of translation initiation

Activation of RegB endoribonuclease by S1 ribosomal protein requires an 11 nt conserved sequence

Structural and Functional Studies of RegB, a New Member of a Family of Sequence-specific Ribonucleases Involved in mRNA Inactivation on the Ribosome

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