| First Author | de la Pe?a JB | Year | 2025 |
| Journal | Pain | Volume | 166 |
| Issue | 9 | Pages | 2091-2102 |
| PubMed ID | 40839605 | Mgi Jnum | J:377316 |
| Mgi Id | MGI:8273672 | Doi | 10.1097/j.pain.0000000000003577 |
| Citation | de la Pena JB, et al. (2025) Ribosome profiling reveals that post-transcriptional control of Nalf1 by heterogeneous nuclear ribonucleoprotein L is required for paclitaxel-induced neuropathic pain. Pain 166(9):2091-2102 |
| abstractText | Sensory neurons are integral to the genesis and maintenance of neuropathic pain. The molecular mechanisms that mediate long-lived changes in their excitability are unclear. Here, we leverage functional genomics approaches to survey changes in RNA abundance and translation in dorsal root ganglion neurons from a mouse model of paclitaxel-induced neuropathic pain. We focus specifically on females as paclitaxel is a first-line therapy for breast cancer. The sequencing data indicate that substantially more changes occur at the level of translation (n = 404) than transcription and decay (n = 109). We discovered that a core subunit of the sodium leak channel (NALCN) channel, auxiliary factor 1 (NALF1), is preferentially translated in response to paclitaxel. This effect is mediated by the RNA-binding protein heterogeneous nuclear ribonucleoprotein L (HNRNP L). Heterogeneous nuclear ribonucleoprotein L binds a 14 base CA-rich element (CARE) in the Nalf1 3' untranslated region (3'UTR). Genetic elimination of either HNRNP L, the Nalf1 CARE motif, or the pore-forming subunit of the nonselective NALCN diminishes pain amplification in vivo. Collectively, these results illustrate that an element situated in a 3'UTR is required for neuropathic pain in female mice. |
