Biology subjects

Anam, M.

Publications and source records attributed to Anam, M..

4 recordsLinked to original sources

bioRxiv2026

Small-RNA Profiling Links 5'-tRNA Halves to Post-therapeutic Disease Persistence and Poor Patient Survival in Glioblastoma

Glioblastoma (GBM) is a highly lethal brain cancer with limited therapeutic durability, where the majority of patients develop recurrent or persistent disease after standard chemoradiotherapy. Meanwhile, tRNA-derived fragments (tRFs) have become increasingly relevant to cancer biology; however, their clinical relevance in GBM remains undefined. Here, we report that a specific family of tRFs, 5-tRNA halves (tiR5s) dominates the small RNA landscape of GBM patient tumors and associates with worse overall survival, post-therapeutic disease persistence, and pro-invasive proteogenomic pathways across two independent GBM patient cohorts. This association between elevated tiR5 levels and therapeutic resistance re-emerges in radiation-resistant GBM xenograft models. Our findings reveal that tiR5s are an underappreciated molecular feature of highly aggressive GBM tumors, supporting further investigation into their biological roles and prognostic utility in GBM. HighlightsO_LItiR5s are the predominant tRF family in primary GBM patient tumors C_LIO_LIElevated tiR5 expression distinguishes primary GBM tumors that develop persistent disease after first-line therapy C_LIO_LIRadiation-resistant GBM PDX models show elevated tiR5 expression C_LIO_LIElevated tiR5 expression associates with poor overall patient survival and pro-invasive molecular programs in GBM patient tumors C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/738483v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@3219d5org.highwire.dtl.DTLVardef@13e09b8org.highwire.dtl.DTLVardef@1f0328borg.highwire.dtl.DTLVardef@867b09_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2026

TRMT6/61A-mediated m1A methylation facilitates human pre-tRNA maturation and prevents surveillance by XRN2

Transfer RNAs (tRNAs) are dynamically regulated by RNA modifications. The conserved TRMT6/61A catalyzes m1A (N1-methyladenosine) deposition at position 58. While TRMT6/61A dysregulation is linked to human diseases, its downstream processing consequences and molecular surveillance mechanisms remain unclear. Here we demonstrate that TRMT6/61A installs m1 A on precursor tRNAs prior to processing. Utilizing a dTAG rapid depletion system, we show that acute loss of TRMT6/61A swiftly reprograms the human tRNAome. Although elongator tRNA fluctuations are buffered by isodecoder redundancy, hypomethylated tRNAiMet is selectively and rapidly degraded by the exoribonuclease XRN2, reducing global protein synthesis and activating ATF4 expression. Furthermore, m1A58 is a prerequisite for tRNA end processing; its absence leads to the aberrant accumulation of unprocessed pre-tRNAs and disrupted tRNA-derived fragment (tRF) populations. Mechanistically, TRMT6/61A facilitates in vitro RNase Z cleavage, likely by promoting proper pre-tRNA folding. Lastly, XRN2 inhibition rescues tRNAiMet levels and reverses growth defects, identifying the XRN2-mediated surveillance of tRNAiMet as a primary driver of the cellular pathology. Collectively, our results uncover a pivotal role for TRMT6/61A-dependent m1A in human tRNA maturation and define the molecular checkpoints essential for translational homeostasis.

genetics↗

bioRxiv2025

Comparative Landscape of Small RNAs in Tissue and Liquid Biopsies for Liver Transplant Outcomes

BackgroundIschemia-reperfusion injury (IRI) is an inevitable consequence of liver transplantation, arising during donor organ procurement and reoxygenation. Severe IRI is a leading contributor to early allograft dysfunction (EAD), a post-transplant complication associated with reduced graft survival. Current postoperative biomarkers provide limited time for intervention, highlighting a need to identify preoperative biomarkers of IRI. Meanwhile, tRNA fragments (tRFs) have emerged as novel biomarkers in various diseases but remain unexplored in the context of liver transplant. ResultsWe performed small RNA sequencing on 96 paired donor liver biopsies from 48 patients to investigate IRI-associated transcript changes. In parallel, 161 donor liver perfusates were analyzed as a non-invasive surrogate for tissue. Across samples, microRNAs (miRNAs) and tRFs were the most abundant. Perfusate expression strongly correlated with biopsies, supporting their value as a non-invasive source of small RNAs. Comparison between post-reperfusion and pre-implantation biopsies revealed that IRI reprogrammed tRF expression. Stratification by clinical outcome showed that patients who developed EAD exhibited specific small RNA signatures in both biopsy and perfusate. Receiver operating characteristic (ROC) analysis revealed a miRNA-based model that achieved an AUC of 0.772, outperforming donor risk index alone (AUC = 0.665), representing a 10.7% increase in discriminative capacity. ConclusionsThese results are the first to establish tRFs as IRI-responsive biomolecules abundant in both donor liver tissue and non-invasive perfusate. In particular, various small RNAs emerged as promising candidate biomarkers for early detection of EAD. These results lay the foundation to further investigate the prognostic utility of tRFs/miRNAs in liver transplantation.

genomics↗

bioRxiv2025

Effects of hCG or GnRH Treatment on Embryonic Mortality and Reproductive Performance in Buchi sheep of Cholistan Desert, Pakistan

The present study was conducted on Buchi sheep at Government livestock farm, Jugaitpeer, district Bahawalpur. The objectives of this study were to investigates the genetic potential, birth and adult body weights, growth and turnover rates, and seasonal reproductive performance, the effect of Dalmazin (PGF2) on synchronization, the effect of GnRH and hCG treatment given on the mating day on pregnancy rate, and embryonic mortality after plasma hormone concentrations and embryo development to improve litter size. Male lambs exhibited significantly higher (P<0.05) birth (3.40 {+/-} 0.16 kg) and adult weights (61.67 {+/-} 0.95 kg) compared to females (3.00 {+/-} 0.00 kg and 39.67 {+/-} 0.41 kg, respectively), along with faster growth and higher turnover rates. Seasonal variations showed superior pregnancy rates in spring (62.83%) but higher reproductive efficiency and lower mortality in autumn. In a second experiment, 30 ewes divided into hCG, GnRH, and control groups. hCG and GnRH groups were mated to ram at synchronized estrus by two injections of 2ml PGF2 analogue (Dalmazin) given at 11 days apart. The control group received only saline. The blood samples were collected from jugular venipuncture (3ml) with a disposable syringe from day 2 to 16 after treatment. Plasma progesterone concentrations detected by ELISA were higher (P<0.05) in sheep as compared with saline treated controls and improved reproductive outcomes. The hCG group showed the best performance with a litter size of 1.28%, no embryonic mortality, and increased twinning and fecundity rates. The GnRH group also demonstrated enhanced reproductive efficiency with a litter size of 1.25% and no embryonic loss. The control group had the lowest reproductive outcomes, including a higher embryonic mortality rate. Overall, hCG proved more effective than GnRH in enhancing progesterone levels, fecundity, and prolificacy in Buchi sheep.

zoology↗