Alternative splice variants of MYH9.
MYH9 encodes a class II nonmuscle myosin heavy chain-A (NMHC-IIA), a widely expressed 1960 amino acid polypeptide, with a translated molecular weight of 220 kDa. The relatively large number of exons (40) that encode NMHC-IIA and the splice variants that have been documented for its two isoforms, MYH10 and MYH14, strongly suggest existence of alternative splicing for MYH9. In the current study, we perform a targeted search for Myh9 splice variants in two separate regions of the heavy chain that encode loop 1 and loop 2 subdomains within which alternative exons in MYH10 and MYH14 splice variants have been identified. The splice variant search was conducted using two strategies: amplification across the suspected exons directly or by amplification of putative splice variants identified through conserved sequence analysis of suspected intronic regions. Within loop 1, two separate insertions of 12 and 41 nucleotides were identified using conserved sequence analysis only. Each of these insertions, located within intron 4, resulted in premature termination of the variant transcript. Within loop 2, a 63-nucleotide-long in-frame insertion was identified using both strategies. The insertion is identical in length and displays 65% sequence identity with its Myh10 counterpart, but differs greatly from the 123-nucleotide-long insertion within Myh14 transcript identified in this study. Both loop 1 and loop 2 variants of Myh9 were detected in the cochlea, with the latter being most abundant in the brain. Expression of loop 1 variants with premature termination codon may reflect an alternate mode of regulating Myh9 expression, while the conserved sequence and selective expression of the loop 2 variant highlight its potential biological importance.
Li
Yan
Y
Laboratory of Molecular Otology, Department of Otolaryngology, New York University School of Medicine, New York, New York 10016, USA.
Lalwani
Anil K
AK
Mhatre
Anand N
AN
D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D005091:Exons; D007438:Introns; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains; D024507:Nonmuscle Myosin Type IIA / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D017385:Sequence Homology
C525088:Myh9 protein, mouse; D020033:Protein Isoforms; D022821:RNA Splice Sites; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains