Abstract
BackgroundNuclear myosin I (NM1) is a nuclear isoform of the well-known “cytoplasmic” Myosin 1c protein (Myo1c). Located on the 11th chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus.Methodology/Principal FindingsIn order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein.Conclusion/SignificanceWe observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes.
Highlights
Myosins are unique proteins that have the ability to transform free chemical energy stored in ATP into mechanical force
Several parameters have been tested in female nuclear myosin 1 (NM1) 2/2 mutants and compared to wild type littermates (Tidal Volume, Inspiratory Capacity, Expiratory Reserve Volume, Vital Capacity, Functional Residual Capacity, Total Lung Capacity, Forced Vital Capacity, Flow Parameters, Forced Expiratory Volume, Peak Expiratory Flow, Static Lung Compliance, Dynamic Lung Compliance, and Lung Resistance)
To prove if Myo1C would mimic the function of NM1 with polymerase II (Pol II), we explored possible interacting partners which would belong to molecular components of Pol II
Summary
Myosins are unique proteins that have the ability to transform free chemical energy stored in ATP into mechanical force. Myosin 1c isoform C is the classic 1063 amino acid ‘‘cytoplasmic’’ form [2]. Myosin 1c isoform B, known as nuclear myosin 1 (NM1), includes 16 extra N-terminal amino acids arising from an upstream exon -1 [5,6]. The newest isoform is myosin 1c, isoform A, which includes additional 35 amino acids on its N-terminal end from an upstream exon -2 and was described to work in the cell nucleus [7]. In mice there have been only two myosin isoforms described – Myo1c and NM1. Nuclear myosin I (NM1) is a nuclear isoform of the well-known ‘‘cytoplasmic’’ Myosin 1c protein (Myo1c). Located on the 11th chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Its nuclear localization signal is localized in the middle of the molecule and directs both Myosin 1c isoforms to the nucleus
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