The study of RNA localization and function has traditionally centered on their roles within the cytoplasm and nucleus of mammalian cells. Recent advances have uncovered a surprising aspect of RNA biology: the presence of specific RNA molecules on the outer surface of mammalian cells. One of the most intriguing discoveries in this area is the identification of glycoRNAs—small non-coding RNAs covalently modified by complex N-glycans—which are synthesized intracellularly but localize to the cell surface. Initial research has revealed that these glycoRNAs may play pivotal roles in cell signaling and immune processes. Nevertheless, their precise functions, regulatory mechanisms, and broader biological significance remain largely unexplored.

A growing body of evidence hints that cell surface glycoRNAs are integral to immune homeostasis and the orchestration of immune cell behavior. Preliminary studies suggest potential roles for glycoRNAs in mediating immune cell adhesion, infiltration, and activation, likely influencing immune surveillance and response to pathogens or disease. Yet, critical questions remain unanswered regarding their origin, transport mechanisms, interactions with cell surface proteins or receptors, and participation in disease processes or immune evasion. The field stands at an exciting intersection, with an urgent need for interdisciplinary efforts to unravel the regulatory and functional landscape of cell surface RNAs.

This Research Topic aims to shed light on the distribution, biosynthesis, and functional implications of cell surface RNAs, particularly glycoRNAs, in the context of immune regulation. We seek to clarify outstanding questions about their biosynthetic pathways, their roles in immune cell communication, and their potential involvement in pathological conditions such as autoimmunity or cancer. Our goal is to create a comprehensive forum for discussion and dissemination of the latest discoveries, foster methodological innovation, and encourage hypothesis-driven research that advances the field.

To gather further insights in the field of cell surface RNAs and their impact on immune responses, we welcome manuscripts addressing, but not limited to, the following themes:

o Mechanisms of RNA glycosylation and cell surface localization with an immunological context.

o Functional roles of glycoRNAs in immune regulation.

o Interactions between cell surface RNAs and immune cell receptors.

o Implications of cell surface RNAs in autoimmune diseases and cancer.

o Methodological advances for the study and detection of extracellular RNAs with an immunological context.

o Evolutionary perspectives and comparative biology of cell surface RNAs.

Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation, for instance in an independent patient population or by PCR, are considered out of scope.

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Cell surface RNAs and immune response