Dataset Information

Conserved small RNA networks link inflammation to pain signaling in mice and men

ABSTRACT: Inflammation may lead to pain, but the underlying mechanisms remain unclear. Here, we identify cooperating small non-coding RNA (sncRNA) signatures including microRNAs (miRs) and transfer RNA fragments (tRFs) that may drive inflammatory pain in both acute and chronic settings. Initiating lipopolysaccharide (LPS)-induced inflammation altered ganglion-specific, time-dependent miRs and tRFs in murine trigeminal (sensory) and superior cervical (sympathetic) ganglia. Indicating conserved pain-related regulatory elements, many of those changes overlapped with those observed in fibromyalgia syndrome (FMS) patient-derived blood cells and keratinocytes. Moreover, cross-species integrative analyses revealed two oppositely correlated sncRNA clusters whose expression ratios distinguished inflammatory from non-inflammatory states and increased during human nociceptor differentiation. Further suggesting functional roles in pain modulation, these pain-related sncRNAs targeted distinct long RNAs expressed in pain- and cholinergic-related states. Importantly, these sncRNAs and their associated transcripts were validated in datasets from both a murine spinal nerve injury model and synovium samples from osteoarthritis patients with varying pain intensities. Our findings reveal that specific miRs and tRFs act as conserved regulators of nociceptive signaling across species, tissues and pain modalities. Further, this work reveals new understanding of the molecular underpinnings of pain and highlights the notion that mammalian pain- and cholinergic-related sncRNAs actively contribute to the shift from inflammation to peripheral nervous system pain, including fibromyalgia pain.

ORGANISM(S): Mus musculus

PROVIDER: GSE303093 | GEO | 2025/08/24

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The ongoing pandemic of coronavirus disease 2019 (COVID-19), which results from the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a significant global public health threat, with molecular mechanisms underlying its pathogenesis largely unknown. Small non-coding RNAs (sncRNAs) are known to play important roles in almost all biological processes. In the context of viral infections, sncRNAs have been shown to regulate the host responses, viral replication, and host-virus interaction. Compared with other subfamilies of sncRNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), tRNA-derived RNA fragments (tRFs) are relatively new and emerge as a significant regulator of host-virus interactions. Using T4 PNK‐RNA‐seq, a modified next‐generation sequencing (NGS), we recently found that nasopharyngeal swabs (NPS) samples from SARS-CoV-2 positive and negative subjects show a significant difference in sncRNA profiles. There are about 166 SARS-CoV- 2-impacted sncRNAs. Among them, tRFs are the most significantly affected and almost all impacted tRFs are derived from the 5’-end of tRNAs (tRF5). Using a modified qRT-PCR, which was recently developed to specifically quantify tRF5s by isolating the tRF signals from its corresponding parent tRNA signals, we validated that tRF5s derived from tRNA GluCTC (tRF5-GluCTC), LysCTT (tRF5-LysCTT), ValCAC (tRF5-ValCAC), CysGCA (tRF5-CysGCA) and GlnCTG (tRF5-GlnCTG) are enhanced in NPS samples of SARS-CoV2 patients and SARS-CoV2-infected airway epithelial cells. In addition to host-derived ncRNAs, we also identified several sncRNAs derived from the virus (svRNAs), among which a svRNA derived from CoV2 genomic site 346 to 382 (sv-CoV2-346) has the highest expression. The induction of both tRFs and sv-CoV2-346 has not been reported previously, as the lack of the 3’-OH ends of these sncRNAs prevents them to be detected by routine NGS. In summary, our studies demonstrated the involvement of tRFs in COVID-19 and revealed new CoV2 svRNAs.

Dataset Information

Conserved small RNA networks link inflammation to pain signaling in mice and men

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets