Zeynep Baharoglu

Zeynep Baharoglu

@zeynepbaharoglu.bsky.social

RNA modifications, antibiotic tolerance, bacterial stress, non coding RNAs, Vibrio cholerae. EPICS lab - Institut Pasteur & EGM (IBPC, CNRS)

2.2K followers1.3K following512 posts

Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Methyltransferase RsmB chaperones E. coli ribosome assembly by orchestrating the recruitment of ribosomal proteins www.science.org/doi/10.1126/...

science.orgMethyltransferase RsmB chaperones E. coli ribosome assembly by orchestrating the recruitment of ribosomal proteinsRibosomal RNA modification enzymes increase cellular fitness, but it’s little known whether this benefit arises from rRNA modification or a chaperone function of the modification enzyme. Here, we show...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Ribosome roadblocks and traffic controllers in bacteria 🦠 journals.asm.org/doi/10.1128/...

journals.asm.orgRibosome roadblocks and traffic controllers in bacteria | Microbiology and Molecular Biology ReviewsSUMMARYProtein synthesis by ribosomes proceeds through the sequential stages of initiation, elongation, termination, and ribosome recycling. In most bacteria, coupled transcription-translation enhances the efficiency of transcription but limits opportunities to repair or eliminate faulty mRNAs, thereby increasing the likelihood that ribosomes encounter incomplete or damaged transcripts. Furthermore, mRNA integrity can be compromised by transcriptional errors, abortive transcription, nucleolytic cleavage, or chemical damage. Translation of such defective transcripts, as well as other hard-to-translate mRNAs, can impede elongation or termination, resulting in stalled ribosome complexes that sequester ribosomes and tRNAs, thereby reducing their availability for subsequent rounds of translation. To maintain translation capacity, bacteria employ dedicated ribosome rescue and quality control pathways that resolve stalled complexes and promote the turnover of aberrant mRNAs and nascent polypeptides. Here, we summarize the molecular mechanisms underlying bacterial ribosome stalling, describe the pathways that rescue stalled ribosomes, and discuss current technologies for detecting ribosome stalling. We also highlight the physiological roles of programmed ribosome stalling and explore the potential of ribosome rescue pathways as druggable sites.
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Growth-dependent tRNA reprogramming and codon bias link translation to metabolic state in Enterococcus faecalis 🦠 journals.asm.org/doi/10.1128/...

journals.asm.orgGrowth-dependent tRNA reprogramming and codon bias link translation to metabolic state in Enterococcus faecalis | mBioEnterococcus faecalis is a common cause of hospital-acquired infections. Despite its clinical importance, a comprehensive understanding of the organism’s physiology and adaptation to environmental cha...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Depletion of the essential CCA-adding enzyme in Mycobacterium tuberculosis leads to selective reprogramming of the DNA damage response and a hyper-mutator phenotype 🦠 link.springer.com/article/10.1...

link.springer.comDepletion of the essential CCA-adding enzyme in Mycobacterium tuberculosis leads to selective reprogramming of the DNA damage response and a hyper-mutator phenotype - Microbial Cell FactoriesThe CCA-adding enzyme, essential for tRNA maturation in Mycobacterium tuberculosis, was considered a potential drug target against multidrug-resistant tuberculosis. We investigated the consequences of...

Zeynep Baharoglu reposted

Frances Yap
@ribo1214.bsky.social

Visualization of co-transcriptional binding of an E. coli rRNA methyltransferase RsmB and importance of rsmB in cellular fitness. #RNASky www.science.org/doi/10.1126/...

science.orgMethyltransferase RsmB chaperones E. coli ribosome assembly by orchestrating the recruitment of ribosomal proteinsRibosomal RNA modification enzymes increase cellular fitness, but it’s little known whether this benefit arises from rRNA modification or a chaperone function of the modification enzyme. Here, we show...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

After tRNA, rRNA, mRNA, RluA apparently also modifies phage RNA (E. coli) 🦠 A host enzyme pseudouridylates an RNA bacteriophage genome and accelerates virus production www.biorxiv.org/content/10.6...

biorxiv.orgA host enzyme pseudouridylates an RNA bacteriophage genome and accelerates virus productionRNA modifications are prevalent and potent regulators of gene expression across all domains of life. However, whether they exist in bacteriophages and whether they impact phage-host interactions are l...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Unexpected ribosome turnover during prolonged translation inhibition www.biorxiv.org/content/10.6...

biorxiv.orgUnexpected ribosome turnover during prolonged translation inhibitionEukaryotes use several distinct quality control pathways to resolve aberrant ribosomes and mRNAs. For example, the no-go decay mRNA pathway is stimulated after ribosome collisions caused by stalled ribosomes translating damaged or truncated mRNAs. Separate decay pathways for non-functional 40S and 60S subunits containing rRNA mutations affecting decoding and peptidyl transferase activity, respectively, have also been elucidated. To our knowledge, whether eukaryotes have evolved a quality control pathway to sense and process globally stalled ribosomes is unclear; however, such a pathway would be advantageous to eukaryotes during exposure to natural elongation inhibitors such as ricin and diphtheria toxin. Here, we test how prolonged robust inhibition of elongation using a high dose of cycloheximide (CHX) affects ribosome turnover. Despite no decrease in cell viability and that mammalian ribosomes have been classically characterized of having a half-life of 3-5 days, a single 24 hr high dose of CHX resulted in drastically shortened half-lives (<24 hr) of 28S and 18S rRNA in A549 cells. A ∼2-fold reduction in nearly all ribosome species was observed by polysome analysis in HeLa and A549 cells after prolonged CHX treatment. Depletion of ribosomes was also evident when assessing ribosomal proteins from both the 40S and 60S subunits by Western blot. Literature supports that ribosomes can be degraded by autophagy and the ubiquitin (Ub)-proteasome system. Upon testing inhibitors of both pathways, only proteasome inhibitors ( i.e. , MG132 and bortezomib) rescued both rRNA and ribosomal protein levels. Proteasome inhibitors also rescued ribosome levels in polysome profiling experiments. Remarkably, rRNA levels were not rescued during CHX treatment when co-treated with the Ub activating enzyme E1 inhibitor, TAK243. Polysome analysis also showed that the high prolonged dose of CHX did not cause robust accumulation of collided ribosomes compared to control treatments. Proteasome-dependent turnover of rRNA was also observed with high doses of other elongation inhibitors, namely anisomycin, homoharringtonine, and lactimidomycin. The recognition capabilities of the pathway were further expanded as we observed that 80S ribosomes not trapped on the mRNA were also targeted for degradation by the proteasome. Together, our findings define the framework of a regulatory pathway in mammalian cells that degrades both ribosomal subunits in response to prolonged periods of robust elongation inhibition. We refer to this novel pathway as the Global Ribosome Instability Pathway (GRIP). ### Competing Interest Statement The authors have declared no competing interest. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM146924, T32GM086252, T32GM141955
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

The ABC-F protein Uup, Rescues Stalled Ribosomal Termination Complexes to Modulate DNA Maintenance 🦠https://www.biorxiv.org/content/10.64898/2026.10.08.757592v1

biorxiv.orgThe ABC-F protein Uup, Rescues Stalled Ribosomal Termination Complexes to Modulate DNA MaintenanceThe cytosolic ATP-binding cassette F (ABC-F) family modulates ribosomal activity in eukaryotes and prokaryotes. Although they all bind to the E site of the ribosome, some bacterial ABC-Fs confer resis...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

EF-P-resolved ribosome stalling and collision trigger Rae1-mediated mRNA decay 🦠https://www.biorxiv.org/content/10.64898/2026.10.09.757949v2 Rae1 cleaves mRNAs with ribosomes stalled on truncated transcripts lacking a stop-codon in B. subtilis

biorxiv.orgEF-P-resolved ribosome stalling and collision trigger Rae1-mediated mRNA decayRibosome stalling compromises proteome integrity and cellular fitness, and requires efficient mechanisms to eliminate problematic mRNAs and rescue blocked ribosomes. We previously identified Rae1 as an endoribonuclease that cleaves mRNAs at the tail end of stalled ribosomes to promote mRNA degradation in Bacillus subtilis. Here, we show that Rae1 has a broader role in the quality control of mRNAs that encounter translation problems. Global 5-end sequencing identified 31 previously unknown Rae1 cleavage sites, many of them associated with ribosome pausing at polyproline motifs in the absence of elongation factor P (EF-P). We also demonstrate that Rae1 cleaves mRNAs with ribosomes stalled on truncated transcripts lacking a stop-codon (non-stop mRNAs), provided that the transcript is sufficiently long to accommodate multiple collided ribosomes. Rae1 cleavage depends on a cytosine-poor context at the cut site, showing that both ribosome collisions and RNA sequence at the cleavage site govern the ability of Rae1 to promote the removal of stalled ribosomes from mRNA. ### Competing Interest Statement The authors have declared no competing interest.
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

The SOS response acts as a regulatory switch that balances helicase anti-recombination with transcription–replication conflict resolution activities in Escherichia coli 🦠https://academic.oup.com/g3journal/article/16/10/jkag205/8746606

academic.oup.comThe SOS response acts as a regulatory switch that balances helicase anti-recombination with transcription–replication conflict resolution activities in Escherichia coliAbstract. Transcription–replication conflicts are a major source of genome instability, particularly at highly transcribed ribosomal RNA genes, where RNA p
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Initiation codon context governs translation-coupled mRNA decay and coordinated expression in the human parasite Leishmania www.biorxiv.org/content/10.6...

biorxiv.orgInitiation codon context governs translation-coupled mRNA decay and coordinated expression in the human parasite LeishmaniaIn the absence of canonical, promoter-based transcriptional regulation, Leishmania has evolved alternative regulatory mechanisms for adaptive gene expression, including post-transcriptional control vi...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

An L-threonine-inducible biosensor derived from the tryptophan-repressed trp promoter of Escherichia coli for high-throughput screening of L-threonine overproducers www.biorxiv.org/content/10.6...

biorxiv.orgAn L-threonine-inducible biosensor derived from the tryptophan-repressed trp promoter of Escherichia coli for high-throughput screening of L-threonine overproducersL-Threonine is an essential amino acid widely used in the feed, food, and pharmaceutical industries, and microbial fermentation is now the dominant route for its production. Further increases in produ...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

A type VI secretion ADP-ribosyltransferase Rhs toxin selectively modifies charged tRNAThr(GGU) anticodon loops to block ACC codon decoding academic.oup.com/nar/article/...

academic.oup.comA type VI secretion ADP-ribosyltransferase Rhs toxin selectively modifies charged tRNAThr(GGU) anticodon loops to block ACC codon decodingAbstract. The type VI secretion system (T6SS) is a sophisticated machine that uses a contractile mechanism to deliver antibacterial toxins into neighboring

Zeynep Baharoglu reposted

STCmicrobeblog
@stcmicrobeblog.bsky.social

#RNASky #MicroSky

Jörg Stülke@joergstuelke.bsky.social

Identification of a novel RNA-modifying enzyme! RlmS! #SubtiWiki www.pnas.org/doi/10.1073/...

pnas.orgActivity-based profiling of bacterial RNA-modifying enzymes reveals species-specific 5-methyluridine modification in Bacillus subtilis 23S rRNA | PNASRNA modifications play an important role in biological processes. Mapping the diversity of RNA chemistry and studying the biological function of in...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Loss of restriction-modification methyltransferases drives persistence to fluoroquinolones in Pseudomonas aeruginosa www.biorxiv.org/content/10.6...

biorxiv.orgLoss of restriction-modification methyltransferases drives persistence to fluoroquinolones in Pseudomonas aeruginosaThe resurgence of phage therapy has renewed interest in the interplay between phage resistance and antibiotic susceptibility and has stimulated research in the emergent field of non-canonical cellular...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

An RNA Language Model trained on sequence alone reveals the structural logic of Internal Ribosome Entry Sites www.biorxiv.org/content/10.6...

biorxiv.orgAn RNA Language Model trained on sequence alone reveals the structural logic of Internal Ribosome Entry SitesMillions of RNA sequences are readily available, but the structures that determine their function are not. Picornaviruses initiate translation through Internal Ribosome Entry Sites (IRESes), RNA eleme...

Zeynep Baharoglu reposted

STCmicrobeblog
@stcmicrobeblog.bsky.social

ribosomologists take note👇 just button up your CsdA coat if you get too cold... #MicroSky

Maria Hondele@mariahondele.bsky.social

Now on bioRxiv 👇 www.biorxiv.org/content/10.6...

biorxiv.orgA bacterial nucleolus for cold adaptationCompartmentalisation enables cells to spatially organise essential biochemical processes. This is exemplified by the eukaryotic nucleolus, which concentrates the machinery for ribosome biogenesis. Bac...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

16S rRNA Modifications Are Dispensable for Viability but Collectively Optimize Ribosome Biogenesis and Translation Initiation in Escherichia coli www.biorxiv.org/content/10.6...

biorxiv.org16S rRNA Modifications Are Dispensable for Viability but Collectively Optimize Ribosome Biogenesis and Translation Initiation in Escherichia coliRibosomal RNAs contain numerous conserved nucleotide modifications, yet the functional importance of most of these modifications remains unclear. In Escherichia coli , deletion of individual 16S rRNA ...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Single-molecule nanopore sequencing reveals spatial coordination of rRNA modifications in human ribosomes www.biorxiv.org/content/10.6...

biorxiv.orgSingle-molecule nanopore sequencing reveals spatial coordination of rRNA modifications in human ribosomesRibosomal RNA has a high density of epitranscriptomic modifications essential for faithful translation, and their levels vary across cell types and in disease. Typically, rRNA modifications are quanti...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Pyridoxal-phosphate-dependent biosynthesis of aminovaleramide by AvaS in tRNA 🦠💫 Discovery of AvaS, the enzyme cqtqlyzing ava2C modificqtion on tRNA-ile www.nature.com/articles/s41...

nature.comPyridoxal-phosphate-dependent biosynthesis of aminovaleramide by AvaS in tRNA - Nature Chemical BiologySun, Wu et al. identify AvaS as a pyridoxal-phosphate-dependent RNA-modifying enzyme, producing the tRNA modification ava2C from k2C in bacteria and plants and linking RNA chemistry to translational r...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

Full-length transcriptomics and proteomics reveal how genome minimization reshapes gene expression in synthetic bacteria 🦠 www.biorxiv.org/content/10.6...

biorxiv.orgFull-length transcriptomics and proteomics reveal how genome minimization reshapes gene expression in synthetic bacteriaJCVI-syn1.0 (Syn1.0) and JCVI-syn3A (Syn3A), genetically synthetic and genome-reduced versions of the naturally occurring bacterium Mycoplasma mycoides, are landmark platforms for defining the gene se...

Zeynep Baharoglu reposted

STCmicrobeblog
@stcmicrobeblog.bsky.social

(pneumococcus) cell divisionists take note👇 a super 🧵 for #MicroSky

Jan-Willem Veening@veeninglab.com

I hadn't thought about the problem of division site selection in a long time. Really cool to see these new studies shining fresh light on such a fundamental question. Especially checkout this work by @aducret.bsky.social & Christophe Grangeasse: doi.org/10.1038/s415...

doi.orgLocal peptidoglycan composition defines division site selection in Streptococcus pneumoniae - Nature MicrobiologySequential peptidoglycan carboxylase activity of DacA and DacB generates a local peptidoglycan signature that recruits MapZ and establishes the division site at the Streptococcus pneumoniae cell equat...
Zeynep Baharoglu
@zeynepbaharoglu.bsky.social

A generalized growth law for translation- and transcription-targeting antibiotics captures drug interactions 🦠💊 www.biorxiv.org/content/10.6...

biorxiv.orgA generalized growth law for translation- and transcription-targeting antibiotics captures drug interactionsBacterial growth laws quantitatively connect intracellular resource allocation to growth rate, enabling accurate predictions of physiology and antibiotic responses. Yet these laws have been rigorously...

Zeynep Baharoglu reposted

Ronald Breaker
@ronbreaker.bsky.social

Our new paper in PNAS reports the presence of Na+ and Li+ #aptamer RNAs in mammals. The latter hints at natural roles for #lithium in humans and provides direct links to #BipolarDisorder. Now seeking funding to study Li+ biology and create new therapeutics.