Translatomics for rRNA, ac4C, and glioblastoma
Recent Publications Harnessing the Power of Translatomics
Every week we provide a digest of a small number of recent interesting papers in the field of translatomics.
In this week’s Sunday papers,
- Vaitkevičius et al. find that the exonuclease DinG degrades unprocessed ribosomal RNAs during ribosome assembly, acting as a quality control factor that removes defective rRNA and prevents incorporation into translating ribosomes.
- Qin et al. find that ribosomal ac4C modifications dynamically accumulate during ribosome maturation and fluctuate in response to environmental stress to actively fine-tune protein synthesis.
- Lin et al. find that the enzyme NAT10 drives glioblastoma progression by applying ac4C modifications to specific oncogenic mRNAs, boosting their translation and highlighting NAT10 as a promising therapeutic target.
The DinG exonuclease acts as a primary quality controller to remove unprocessed ribosomal RNAs
Nucleic Acids Research, 2026
Vaitkevičius, K. and Johansson, J.
This paper investigates the role of the DinG protein in ribosome biogenesis and quality control in Listeria monocytogenes. Ribosomal RNA (rRNA) maturation is a multistep process that requires correct folding, processing of precursor rRNAs, and coordinated assembly with ribosomal proteins. Defects in this process generate immature ribosomal subunits containing unprocessed rRNA, which must be removed to maintain translational efficiency.
The authors show that DinG functions as a 3′→5′ exonuclease that selectively targets immature rRNA. Genetic suppressor analysis revealed that mutations in dinG restore growth defects in strains lacking the DEAD-box RNA helicase CshC, suggesting that DinG activity becomes detrimental when ribosome assembly is impaired. Biochemical assays showed that purified DinG degrades precursor rRNAs but not mature rRNAs, indicating substrate specificity. In vivo and ex vivo experiments further demonstrated that loss of DinG stabilizes rRNA precursors, whereas active DinG degrades unprocessed 16S and 23S rRNAs, supporting its role as a primary quality control nuclease in ribosome biogenesis.
Polysome profiling showed that deletion of cshC dramatically reduces mature 70S ribosomes and polysomes while increasing immature 30S and pre-50S subunits. When dinG is also deleted, the levels of actively translating 70S ribosomes and polysomes increase, partially restoring the ribosome profile and improving translation efficiency compared with the ΔcshC mutant. However, translation remains lower than in wild type.
Together, the study proposes that DinG initiates the degradation of faulty rRNA during defective ribosome assembly, thereby functioning as an early ribosome quality control factor.
Learn more about EIRNABio’s polysome profiling services here.
Locus-specific quantification reveals dynamics of ribosomal ac4C modifications
New Biotechnology, 2026
Qin, N., Wang, Y., Yuan, Q., Chen, L. and Qu, G.-S.
This paper explores the role of N4-acetylcytidine (ac4C) chemical modifications in ribosomal RNA. Because the precise dynamics of ac4C have historically been difficult to track, the researchers developed and validated several locus-specific quantification methods (including an approach called ac4C-Sanger, as well as High-Resolution Melting (HRM) and SELECT) to accurately map these modifications in yeast (Saccharomyces cerevisiae).
Using these tools, the study reveals that ac4C modifications are not static structural features; rather, they accumulate progressively as the ribosome matures. Crucially, the researchers discovered that the levels of these modifications are highly dynamic and responsive to environmental changes, such as cellular growth phases and heat stress. These stress-induced fluctuations were found to correlate with changes in the accuracy and efficiency of protein translation. Polysome profiling showed that early-stage cells at 40°C have reduced 60S, monosome, and polysome peaks and a significantly lower polysome-to-monosome ratio compared to 30°C, indicating impaired translation initiation and/or ribosome loading under heat stress. Additionally, the study uncovered a complex interplay between ac4C and other types of nearby RNA modifications during ribosome biogenesis.
Ultimately, the work establishes ribosomal ac4C as an adaptive modification that helps cells fine-tune protein synthesis in response to their environment, while also providing the scientific community with new techniques to study these intricate molecular dynamics.
Learn more about EIRNABio’s polysome profiling services here.
NAT10-mediated ac4C modifications regulate glioblastoma progression
Cell Death & Disease, 2026
Lin, L., Xiong, Y., Guo, Y., Tu, Z., Luo, P., Fang, Z., Zhang, L., Huang, K. and Wu, L.
This paper explores the oncogenic role of N-acetyltransferase 10 (NAT10), the sole enzyme catalyzing N4-acetylcytidine (ac4C) mRNA modifications, in glioblastoma (GBM). NAT10 is significantly overexpressed in GBM, strongly correlating with disease progression and poor patient survival. Functionally, elevated NAT10 drives cell proliferation and migration in vitro, and accelerates tumor growth in vivo.
To uncover NAT10’s underlying mechanism, researchers utilized a multi-omics approach. By integrating RNA-seq with acRIP-seq, they identified the mRNA of BOC (a cell adhesion molecule) as a primary, hyper-acetylated target. Furthermore, Ribo-seq and polysome profiling revealed that NAT10 drives progression predominantly at the translational level rather than via massive transcriptional shifts. While global translation remains stable following NAT10 depletion, ac4C deposition selectively promotes ribosomal engagement for a specific subset of oncogenic transcripts. For BOC specifically, NAT10 enhances both its overall mRNA stability and its translational efficiency, directly fuelling tumor progression.
Additionally, the authors link this regulation to the hypoxic (low-oxygen) tumor microenvironment. The hypoxia-inducible transcription factor HIF1α directly binds the NAT10 promoter, upregulating its expression and amplifying its ac4C activity. Crucially, the study shows that pharmacological inhibition of NAT10 successfully neutralizes its enzymatic function, particularly in hypoxic conditions, showcasing its therapeutic target potential for GBM.
Ultimately, the paper maps a novel HIF1α/NAT10/BOC axis in GBM oncogenesis, establishing NAT10-mediated RNA modification as a critical driver of the disease and highlighting it as a promising, actionable therapeutic target.
Learn more about EIRNABio’s RNA-seq, ribosome profiling, and polysome profiling services here.
