Nuclear myosin VI enhances RNA polymerase II-dependent transcription.
Myosin VI is the only myosin that moves toward the minus end of actin filaments, suggesting a unique biological function. Here, we show that myosin VI is present in the nucleus of mammalian cells where it colocalizes with newly transcribed mRNA and with RNA polymerase II (RNAPII) and is detected in the RNAPII complex. The colocalization and interaction of myosin VI with RNAPII require transcriptional activity. Chromatin immunoprecipitation (ChIP) demonstrates that myosin VI is recruited to the promoter and intragenic regions of active genes, encoding urokinase plasminogen activator (uPA), eukaryotic initiation factor 6 (p27/eIF6), and low-density lipoprotein receptor (LDLR), but not to noncoding, nonregulatory intergenic regions. Downregulation of myosin VI reduces steady-state mRNA levels of these genes in vivo, and antibodies to myosin VI reduce transcription in vitro. We suggest that myosin VI modulates RNAPII-dependent transcription of active genes, implicating the possibility of an actin-myosin based mechanism of transcription.
Vreugde
Sarah
S
Molecular Histology and Cell Growth Unit, DIBIT, Via Olgettina 58, Milano 20132, Italy. vreugde.sarah@hsr.it
Ferrai
Carmelo
C
Miluzio
Annarita
A
Hauben
Ehud
E
Marchisio
Pier Carlo
PC
Crippa
Massimo P
MP
Bussi
Mario
M
Biffo
Stefano
S
D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D012319:RNA Polymerase II / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; C089785:myosin VI; D012319:RNA Polymerase II; D018995:Myosin Heavy Chains