Stem-Loop Structures within mRNA Coding Sequences Activate Translation Initiation and Mediate Control by Small Regulatory RNAs

Jagodnik, Jonathan; Chiaruttini, Claude; Guillier, Maude

doi:10.1016/j.molcel.2017.08.015

Cited by 58 publications

(60 citation statements)

References 48 publications

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“…RBPs typically do not access primary nucleotide sequence information in regions of double-stranded structure but rather recognize sequences in single-stranded regions (66). The secondary structures of transcripts have been found to impact translational efficiency (67)(68)(69)(70). In our study, single-stranded regions of the SLII of COXVI 3'UTR were important for sugar-based regulation, as mutations that altered either the single-strand loop or bubble of SLII impacted the response.…”

Section: Comparison Of the Transcriptional Profiles Of Monomorphic Bfmentioning

confidence: 67%

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Qiu

Shankar

Noorai

et al. 2018

Preprint

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The ability to adapt to varying nutrient availability in changing environments is critical for successful parasitism. The lifecycle stages of the African trypanosome, Trypanosoma brucei, that infect the host mammalian bloodstream utilize glucose exclusively for ATP production. The finding that trypanosomes also inhabit other tissues that frequently contain lower glucose concentrations suggests blood stage parasites may have to respond to a dynamic environment with changing nutrient availability in order to survive. However, little is known about how the parasites coordinate gene expression with nutrient availability. Through transcriptome analysis, we have found blood stage parasites deprived of glucose alter gene expression in a pattern similar to transcriptome changes triggered by other stresses. A surprisingly low concentration of glucose (<10 μM) was required to initiate the response. To further understand the dynamic regulation of gene expression that occurs in response to altered glucose availability in the environment, we have interrogated the 3'UTR of cytochrome c oxidase subunit VI, a known lifecycle stage regulated gene, and have identified a stem-loop structure that confers glucose-responsive regulation at the translational level.

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Section: Comparison Of the Transcriptional Profiles Of Monomorphic Bfmentioning

confidence: 67%

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Qiu

Shankar

Noorai

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…We and others have been interested in two sequence-similar sRNAs, OmrA and OmrB, which act on multiple target mRNAs to regulate outer membrane and surface protein expression (Guillier & Gottesman, 2006Holmqvist et al, 2010;Mika & Hengge, 2014;Brosse et al, 2016;Jagodnik et al, 2017). Their genes (Argaman et al, 2001;Wassarman et al, 2001;Vogel et al, 2003) are transcriptionally activated by the OmpR-EnvZ two-component system, e.g., under high osmolarity conditions (Guillier & Gottesman, 2006;Brosse et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Hfq‐dependent mRNA unfolding promotes sRNA ‐based inhibition of translation

et al. 2019

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Small RNAs post‐transcriptionally regulate many processes in bacteria. Base‐pairing of sRNAs near ribosome‐binding sites in mRNAs inhibits translation, often requiring the RNA chaperone Hfq. In the canonical model, Hfq simultaneously binds sRNAs and mRNA targets to accelerate pairing. Here, we show that the Escherichia coli sRNAs OmrA and OmrB inhibit translation of the diguanylate cyclase DgcM (previously: YdaM), a player in biofilm regulation. In OmrA/B repression of dgcM, Hfq is not required as an RNA interaction platform, but rather unfolds an inhibitory RNA structure that impedes OmrA/B binding. This restructuring involves distal face binding of Hfq and is supported by RNA structure mapping. A corresponding mutant protein cannot support inhibition in vitro and in vivo; proximal and rim mutations have negligible effects. Strikingly, OmrA/B‐dependent translational inhibition in vitro is restored, in complete absence of Hfq, by a deoxyoligoribonucleotide that base‐pairs to the biochemically mapped Hfq site in dgcM mRNA. We suggest that Hfq‐dependent RNA structure remodeling can promote sRNA access, which represents a mechanism distinct from an interaction platform model.

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“…One such important gene feature is the 5’ untranslated region (5’ UTR), which contains the Shine-Dalgarno (SD) sequence within the ribosome binding site (RBS), and therefore can serve as a translation regulator [1-5]. For example, 5’ UTR interactions with cis and trans elements, such as complementary sequences within the UTR or coding sequence, small RNAs (sRNAs), and RNA-binding proteins, can modulate protein synthesis by blocking or improving accessibility to the RBS [6-9]. Importantly, it has been shown in Escherichia coli and other bacteria that transcription and translation are physically coupled, and thus 5’ UTR-mediated modulation of translation could have repercussions on transcription rate as well [10-14].…”

Section: Introductionmentioning

confidence: 99%

The impact of leadered and leaderless gene structures on translation efficiency, transcript stability, and predicted transcription rates inMycobacterium smegmatis

Nguyen

Vargas-Blanco

Roberts

et al. 2019

Preprint

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16Regulation of gene expression is critical for the pathogen Mycobacterium tuberculosis to tolerate 17 stressors encountered during infection, and for non-pathogenic mycobacteria such as 18Mycobacterium smegmatis to survive stressors encountered in the environment. Unlike better 19 studied models, mycobacteria express ~14% of their genes as leaderless transcripts. However, the 20 impacts of leaderless transcript structures on mRNA half-life and translation efficiency in 21 mycobacteria have not been directly tested. For leadered transcripts, the contributions of 5' UTRs 22 to mRNA half-life and translation efficiency are similarly unknown. In both M. tuberculosis and 23 M. smegmatis, the essential sigma factor, SigA, is encoded by an unstable transcript with a 24 relatively short half-life. We hypothesized that sigA's long 5' UTR caused this instability. To test 25 this, we constructed fluorescence reporters and then measured protein abundance, mRNA 26 abundance, and mRNA half-life. From these data we also calculated relative transcription rates. 27We found that the sigA 5' UTR confers an increased transcription rate, a shorter mRNA half-life, 28 and a decreased translation rate compared to a synthetic 5' UTR commonly used in mycobacterial 29 expression plasmids. Leaderless transcripts produced less protein compared to any of the leadered 30 transcripts. However, translation rates were similar to those of transcripts with the sigA 5' UTR, 31 and the protein levels were instead explained by lower transcript abundance. A global comparison 32 of M. tuberculosis mRNA and protein abundances failed to reveal systematic differences in 33 protein:mRNA ratios for natural leadered and leaderless transcripts, consistent with the idea that 34 variability in translation efficiency among mycobacterial genes is largely driven by factors other 35 than leader status. The variability in mRNA half-life and predicted transcription rate among our 36 constructs could not be explained by their different translation efficiencies, indicating that other 37 factors are responsible for these properties and highlighting the myriad and complex roles played 38 by 5' UTRs and other sequences downstream of transcription start sites. 39 40 41 5' UTRs can also regulate gene expression by altering mRNA turnover rates. This can be a 57 consequence of altered translation rates, as impairments to translation often lead to faster mRNA 58 decay [16][17][18][19][20][21][22]. In other cases, mRNA stability is directly affected by sRNA binding to 5' UTRs or 59 by UTR secondary structure [9,[23][24][25][26][27][28]. In E. coli, the half-life of the short-lived transcript bla can 60 be significantly increased when its native 5' UTR is replaced with the 5' UTR of ompA, a long-61 lived transcript [29][30][31]. Conversely, deletion of ompA's native 5' UTR decreased its half-life by 62 5-fold [30]. The longevity conferred by the ompA 5' UTR was attributed to the presence of a non-63 specific stem-loop as well as the specific RBS sequence [30][31][32]. Secondary ...

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Stem-Loop Structures within mRNA Coding Sequences Activate Translation Initiation and Mediate Control by Small Regulatory RNAs

Cited by 58 publications

References 48 publications

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Identification of a post-transcriptional regulatory element that responds to glucose in the African trypanosome

Hfq‐dependent mRNA unfolding promotes sRNA ‐based inhibition of translation

The impact of leadered and leaderless gene structures on translation efficiency, transcript stability, and predicted transcription rates inMycobacterium smegmatis

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