Widespread Presence of Catalytic RNAs in All Domains of Life

Qi, F.; Chen, Y.; Lin, Y.; Chen, Z.; Zhong, Y.; Zhang, F.; Li, K.; Zhao, Y.; Li, M.; Chen, S.; Kruglikov, I.; Yin, W.; Tang, Q.; Chen, J.; Zhang, W.; Lin, H.; Lilley, D.; Kapranov, P.

doi:10.64898/2026.10.26.761763

bioRxiv · 10.64898/2026.10.26.761763

Widespread Presence of Catalytic RNAs in All Domains of Life

Qi, F.·Chen, Y.·Lin, Y.·Chen, Z.·Zhong, Y.·Zhang, F.·Li, K.·Zhao, Y.·Li, M.·Chen, S.·Kruglikov, I.·Yin, W.·Tang, Q.·Chen, J.·Zhang, W.·Lin, H.·Lilley, D.·Kapranov, P.

View original source ↗Export metadata ↓

Abstract

Very few ribozymes have been found in complex eukaryotes. Here, we developed a novel method, AbRiDGed, for highly accurate and sensitive ab initio self-cleaving ribozyme discovery. Our results indicate the existence of millions of self-cleaving ribozymes in humans and other species. We characterized ~150 novel classes of self-cleaving ribozymes, including one class which exhibits noncanonical biochemical properties and widespread presence in all domains of life and appears to play specific functions in complex organisms. These results revealed that the true complexity of the "ribozyme-ome" is several orders of magnitude higher than previously estimated. We demonstrate that newly identified self-cleaving ribozymes influence organismal fitness by regulating gene expression and enhancing transcriptome complexity in vivo. Moreover, these ribozymes hold promise as foundational tools for biotechnological applications, such as direct RNA detection technologies. Overall, catalytic RNAs are prevalent and diverse, and may represent a hidden regulatory layer in various organisms.

Explore related subjects

molecular biology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Qi, F., Chen, Y., Lin, Y., Chen, Z., Zhong, Y., Zhang, F., Li, K., Zhao, Y., Li, M., Chen, S., Kruglikov, I., Yin, W., Tang, Q., Chen, J., Zhang, W., Lin, H., Lilley, D., Kapranov, P.. 2026-10-28. Widespread Presence of Catalytic RNAs in All Domains of Life. https://doi.org/10.64898/2026.10.26.761763

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Sex-based differences in fibrosis markers in human abdominal aortic aneurysms

Background: Abdominal aortic aneurysms (AAA) are a complex degenerative vascular disease. The role of fibrosis in AAA progression is unclear. Our study evaluated the impact of fibroblast activation protein (FAP), collagen, and vimentin on AAA fibrosis and progression. We hypothesized that FAP may influence fibrosis and disease severity in AAA, with potential sex-specific differences. Study Design: Multi-centered transcriptomic analysis of aortic samples from 15 human AAA and 5 non-AAA was performed to evaluate cell-specific fibrosis gene expression profiles. Histopathological and molecular analysis of 26 male and female AAA samples (mAAA and fAAA) and 29 male and female normal abdominal aortas (mNAA and fNAA) was performed to assess whole-tissue fibrosis markers and signaling. Results: Single-cell RNA sequencing (scRNA-seq) analysis identified eight major cell clusters with distinct sex-based distributions. Although vascular smooth muscle cells (VSMCs) and fibroblast clusters had reduced counts in both male and female AAAs, they more highly expressed FAP and COL1A1 genes, particularly in females. Whole-tissue analysis demonstrated elevated extracellular matrix deposits with markedly increased collagen type 1 in both mAAA and fAAA. Alpha-smooth muscle actin (-SMA)-positive VSMCs were also reduced in mAAA and fAAA, but FAP was notably elevated, and robustly in fAAA. FAP-positive fibroblasts in fAAA exhibited increased expression of fibrosis markers, suggesting a unique pro-fibrotic phenotype. Conclusion: Our study reveals a sex-based difference in AAA tissue, with elevated fibrosis markers and increased FAP levels in females, suggesting its significant role in disease progression. These findings underscore the potential of FAP as a unique tissue biomarker for AAAs and warrants further investigation into novel targeted therapies that aim to stabilize AAAs, particularly in female patients.

molecular biology↗

bioRxiv2026

Endonuclease G governs an antiviral RNA surveillance system in budding yeast

Endonuclease G family DNA/RNA nucleases localize to the mitochondrial intermembrane space and prevent escape of mitochondrial DNA to the cytosol or nucleus. While extramitochondrial Endonuclease G also targets nuclear DNA during cell death, RNA regulatory roles of this family remain enigmatic. Here we discover an RNA surveillance system in Saccharomyces cerevisiae governed by Nuc1, the yeast Endonuclease G homolog. This system limits replication of L-A, an RNA mycovirus that endemically infects this organism. Whereas L-A resides in the cytosol, we find that Nuc1's antiviral function requires its mitochondrial intermembrane space localization. To understand Nuc1's indirect antiviral mechanism we investigated its genetic interactions with REX1 and REX2, RNA exonucleases that control 3' end processing of tRNA and rRNA intermediates in the nucleus. We demonstrate that the nuc1{triangleup} antiviral defect is massively amplified by rex1{triangleup} rex2{triangleup} leading to L-A RNA levels that surpass mature rRNAs and overwhelm the cells. NUC1 concurrently controls a pool of mis-processed tRNA and rRNA species that accumulate in rex1{triangleup} rex2{triangleup} mutants. Linking these mis-processed RNAs with L-A control, we show they are significantly reduced in L-A infected cells, suggesting that L-A depletes them to enhance its replication. Our findings identify a previously unrecognized RNA surveillance function of Nuc1 that prevents aberrant rRNA and tRNA species from promoting replication of the L-A mycovirus.

molecular biology↗

bioRxiv2026

Feedback control via H3K9 methylation and siRNA biogenesis autonomously maintains RNAi heterochromatin through continuous low-level transcription

The logic of RNA-based silencing involves nascent RNA molecules that serve as scaffolds to recruit proteins that repress transcription. Despite transcription and silencing being antagonistic, RNA-based recruitment mechanisms have been widely adopted in organisms ranging from yeast to humans. In fission yeast (Schizosaccharomyces pombe), the nuclear RNAi pathway that establishes heterochromatin at pericentromeric repeats to silence transcription exemplifies this paradox. Current models propose that cells reconcile these opposing activities by confining pericentromeric transcription to S phase while maintaining silencing during the rest of the cell cycle. Here, using strand-specific single-molecule RNA FISH (smFISH), we detect forward and reverse pericentromeric transcripts with high sensitivity and single-cell resolution. We find that repeat-associated transcription is rare, heterogeneous and happens independently of cell-cycle control. Instead, transcript production is governed solely by feedback involving small RNA biogenesis and H3K9 methylation. By combining mathematical modeling with experiments, we show that low levels of H3K9me or siRNAs prevent heterochromatin establishment, whereas high levels of H3K9me cause stochastic switching. Our work reveals that the same RNA-based feedback architecture can sample distinct transcriptional regimes, with feedback strength determining how often cells produce transcripts without any external regulatory inputs.

molecular biology↗