3'UTRs Regulate Mouse Ntrk2 mRNA Distribution in Cortical Neurons

J Mol Neurosci. 2020 Nov;70(11):1858-1870. doi: 10.1007/s12031-020-01579-8. Epub 2020 May 19.

Abstract

There are two major isoforms of NTRK2 (neurotrophic receptor tyrosine kinase 2, or TrkB), full-length isoform with tyrosine kinase (TK) domain intact (+) and spliced isoform without tyrosine kinase domain (TK(-)). Within each isoform, there exist subtypes with minor modifications of the protein sequences. In human, the NTRK2 mRNA transcripts encoding TK(+) have same 3'UTRs, while the transcripts encoding subtypes of NTRK2 TK(-) have two completely different 3'UTRs. In mouse, the mRNA transcripts encoding same NTRK2 protein sequence for either TK(+) or TK(-) have long or short 3'UTRs, respectively. The physiological functions of these different 3'UTRs are still unknown. Pilocarpine stimulation increased Ntrk2 mRNA levels in soma, while the increase in synaptosome was smaller. FISH results further showed that mouse Ntrk2 transcripts with different 3'UTRs were distributed differently in cultured cortical neurons. The transcripts with long 3'UTR were distributed more in apical dendrites compared with transcripts with short 3'UTR. Our results provide evidence of non-coding 3'UTR function in regulating mRNA distribution in neurons.

Keywords: 3′UTR; NTRK2; Neuron; mRNA.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • RNA Transport*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Synaptosomes / metabolism

Substances

  • 3' Untranslated Regions
  • Membrane Glycoproteins
  • RNA, Messenger
  • Ntrk2 protein, mouse
  • Protein-Tyrosine Kinases