Premium
New Species of Human Tyrosine Hydroxylase mRNA Are Produced in Variable Amounts in Adrenal Medulla and Are Overexpressed in Progressive Supranuclear Palsy
Author(s) -
Dumas Sylvie,
Le Hir Hervé,
BodeauPéan Sylvie,
Hirsch Etienne,
Thermes Claude,
Mallet Jacques
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67010019.x
Subject(s) - tyrosine hydroxylase , progressive supranuclear palsy , adrenal medulla , biology , alternative splicing , exon , complementary dna , messenger rna , rna splicing , neurodegeneration , endocrinology , gene isoform , medicine , microbiology and biotechnology , rna , genetics , catecholamine , gene , disease , dopamine , atrophy
Alternative splicing of human tyrosine hydroxylase (TH) pre‐mRNA produces four mRNAs leading to four different TH isoforms and is thought to have important regulatory functions. We show that the diversity of TH mRNAs is greater than previously described in the autonomous nervous system: New splice junctions corresponding to the skipping of exon 3 were identified by amplification of cDNA synthesized from pheochromocytoma RNA. In all cases the reading frame was maintained. These species were assayed by RNase protection experiments; their abundance (4–6%) was comparable to that of the previously identified human TH‐3 and ‐4 species in normal adrenal medulla. However, higher levels (11–34%) of these species were found in adrenal medullas of patients suffering from progressive supranuclear palsy. Whether such changes are specific to the disease or the consequences of the stress associated with this severe neurodegeneration remains to be established.