Post-transcriptional Controls in Nociceptive Signaling

Simple item page
dc.contributor.advisorDelk, Nikki
dc.contributor.advisorCampbell, Zachary
dc.contributor.advisorDodani, Sheel
dc.contributor.advisorDelk, Nikki
dc.contributor.advisorDodani, Sheel
dc.contributor.advisorDodani, Sheel
dc.contributor.committeeMemberPalmer, Kelli
dc.contributor.committeeMemberMorcos, Faruck
dc.contributor.committeeMemberMisra, Jyoti
dc.contributor.committeeMemberPalmer, Kelli
dc.creatorKunder, Nikesh Prakash 1991-
dc.creator.orcid0000-0002-8456-7703
dc.date.accessioned2023-05-31T18:57:34Z
dc.date.available2023-05-31T18:57:34Z
dc.date.created2022-12
dc.date.issued2022-12-01T06:00:00.000Z
dc.date.submittedDecember 2022
dc.date.updated2023-05-31T18:57:35Z
dc.description.abstractChronic pain is a condition wherein pain continues beyond the completion of the healing process. It is a debilitating condition that diminishes quality of life and is highly prevalent. Persistent pain is characterized by nociceptor plasticity. Dorsal root ganglion (DRG) neurons are responsible for generating nociceptive signals and undergo plasticity changes following injury. These changes are intimately linked to persistent pain. Translational regulation of mRNA permeates pain plasticity. Yet, the identity of translationally regulated mRNA that mediates plasticity is unknown. In this study, we used ribosome profiling to determine the protein landscape of sensory neurons after a brief exposure to the inflammatory mediators, NGF and IL-6. We observed preferential translation of a variety of transcripts. We focused on two immediate early genes, Arc and c-Fos that play a role in neuronal plasticity. These proteins have two very distinct functions: Arc regulates neuroinflammation while c-Fos regulates neuronal excitability. We also observed ribosomal occupancy on long non- coding RNAs as well as uORF utilization in certain mRNA transcripts. Among the various uORF containing transcripts, we identified a novel peptide generated from a uORF present in the 5ˊUTR of Calca mRNA. This short peptide generated from Calca is responsible for nociceptor sensitization via Gq signaling. Finally, we also identified that the 3’UTRs of preferentially translated mRNA contained a U-rich element for a RNA- binding protein called HuR. This protein contributes to nociceptor firing and mechanical hypersensitivity in mice. Our work provides insights into new key players that govern neuronal functions.
dc.format.mimetypeapplication/pdf
dc.identifier.uri
dc.identifier.urihttps://hdl.handle.net/10735.1/9746
dc.language.isoen
dc.subjectBiology, Molecular
dc.subjectBiology, Neuroscience
dc.titlePost-transcriptional Controls in Nociceptive Signaling
dc.typeThesis
dc.type.materialtext
thesis.degree.collegeSchool of Natural Sciences and Mathematics
thesis.degree.departmentBiology - Molecular and Cell Biology
thesis.degree.disciplineMolecular & Cell Biology
thesis.degree.grantorThe University of Texas at Dallas
thesis.degree.namePHD
thesis.degree.programMolecular and Cell Biology
thesis.degree.schoolSchool of Natural Sciences and Mathematics

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
KUNDER-PRIMARY-2022.pdf
Size:
3.51 MB
Format:
Adobe Portable Document Format
Download

License bundle

Now showing 1 - 4 of 4
No Thumbnail Available
Name:
LICENSE.txt
Size:
1.85 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
PROQUEST_LICENSE.txt
Size:
5.85 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
license.txt
Size:
2 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
proquest_license.txt
Size:
6.38 KB
Format:
Plain Text
Description:
Download

Collections

UTD Theses and Dissertations