TASR-1 regulates alternative splicing of collagen genes in chondrogenic cells.
During the differentiation of chondroprogenitors into mature chondrocytes, the alternative splicing of collagen genes switches from longer isoforms to shorter ones. To investigate the underlying mechanisms, we infected mouse ATDC5 chondroprogenitor cells with retrovirus for stable expression of two closely related SR splicing factors. RT-PCR analysis revealed that TASR-1, but not TASR-2, influenced alternative splicing of type II and type XI collagens in ATDC5 cells. The effect of TASR-1 on splicing could be reversed with the addition of insulin. Results from our microarray analysis of ATDC5 cells showed that TASR-1 and TASR-2 differentially affect genes involved in the differentiation of chondrocytes. Of special interest is the finding that TASR-1 could down-regulate expression of type X collagen, a hallmark of hypertrophic chondrocytes. Immunohistostaining demonstrated that TASR-1 protein is more abundantly expressed than TASR-2 in mouse articular chondrocytes, raising the possibility that TASR-1 might be involved in phenotype maintenance of articular chondrocytes.
Matsushita
Hiroshi
H
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Blackburn
Michael L
ML
Klineberg
Eric
E
Zielinska-Kwiatkowska
Anna
A
Bolander
Mark E
ME
Sarkar
Gobinda
G
Suva
Larry J
LJ
Chansky
Howard A
HA
Yang
Liu
L
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D020219:Chondrogenesis / Q000502:physiology*; D024043:Collagen Type II / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*
D018797:Cell Cycle Proteins; D024043:Collagen Type II; C485446:Fusip1 protein, mouse; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins