tsRNA modifications: An emerging layer of biological regulation in disease.

Background: Transfer RNA (tRNA)-derived small RNA (tsRNA) represents an important and increasingly valued type of small non-coding RNA (sncRNA). The investigation of tRNA and tsRNA modification crosswalks has not only provided novel insights into the information and functions of tsRNA, but has also expanded the diversity and complexity of the tsRNA biological regulation network.

Aim Of Review: Comparing with other sncRNAs, tsRNA biogenesis show obvious correlation with RNA modifications from mature tRNA and harbor various tRNA modifications.

A Novel tsRNA, mG-3' tiRNA Lys, Promotes Bladder Cancer Malignancy Via Regulating ANXA2 Phosphorylation.

Emerging evidence indicates that transfer RNA (tRNA)-derived small RNAs (tsRNAs), originated from tRNA with high abundance RNA modifications, play an important role in many complex physiological and pathological processes. However, the biological functions and regulatory mechanisms of modified tsRNAs in cancer remain poorly understood. Here, it is screened for and confirmed the presence of a novel mG-modified tsRNA, mG-3'-tiRNA Lys (mtiRL), in a variety of chemical carcinogenesis models by combining small RNA sequencing with an mG small RNA-modified chip.

TROP2 translation mediated by dual mA/mG RNA modifications promotes bladder cancer development.

RNA modifications, including adenine methylation (mA) of mRNA and guanine methylation (mG) of tRNA, are crucial for the biological function of RNA. However, the mechanism underlying the translation of specific genes synergistically mediated by dual mA/mG RNA modifications in bladder cancer (BCa) remains unclear. We demonstrated that mA methyltransferase METTL3-mediated programmable mA modification of oncogene trophoblast cell surface protein 2 (TROP2) mRNA promoted its translation during malignant transformation of bladder epithelial cells.

Targeted mA demethylation of ITGA6 mRNA by a multisite dCasRx-mA editor inhibits bladder cancer development.

Introduction: N6-methyladenosine (mA) modification contributes to the pathogenesis and development of various cancers, including bladder cancer (BCa). In particular, integrin α6 (ITGA6) promotes BCa progression by cooperatively regulating multisite mA modification. However, the therapeutic effect of targeting ITGA6 multisite mA modifications in BCa remains unknown.