Deletion of 3'-untranslated region alters the level of mRNA expression of a neurofilament light subunit transgene.
High levels of neurofilament (NF) mRNA expression are attained during early postnatal development and are a major determinant of axonal size. High level NF expression is also dependent upon axonal continuity since NF mRNA levels are down-regulated after nerve transection. This study shows that both postnatal up-regulation and axotomy-induced down-regulation are altered by deletion of 3'-UTR from the mouse light NF subunit (NF-L). Transgenes with (NF-L+) or without (NF-L-) 3'-UTR display similar patterns of neuron-specific expression but differ in their respective levels of expression. Whereas changes in the level of NF-L+ mRNA parallel those of the endogenous mouse NF-L mRNA, changes in the level of NF-L- mRNA differ from the pattern of endogenous NF-L expression during postnatal up-regulation and axotomy-induced down-regulation. Specifically, the NF-L- transgene undergoes a 3-fold aberrant up-regulation between embryonic days 15 (E15) and 18 (E18) and has lost its susceptibility to axotomy-induced down-regulation. Studies of transfected P19 cells show that 3'-UTR deletion leads to a severalfold stabilization of NF-L mRNA and an increase in steady-state mRNA level. The findings support the working hypothesis that the 3'-UTR contains determinants that alter stability and that stabilization of NF-L mRNA regulates the levels of NF-L mRNA in neuronal tissues and cells.
Schwartz
M L
ML
Division of Neuropathology, University of Pennsylvania Medical School, Philadelphia 19104-6079, USA.
Bruce
J
J
Shneidman
P S
PS
Schlaepfer
W W
WW
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000502:physiology; D005314:Embryonic and Fetal Development; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D005865:Gestational Age; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D016254:Mutagenesis, Insertional; D016900:Neurofilament Proteins / Q000096:biosynthesis*; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000096:biosynthesis*; D012584:Sciatic Nerve / Q000502:physiology; D017384:Sequence Deletion; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D014158:Transcription, Genetic
D016900:Neurofilament Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C044882:neurofilament protein L