1. Nuclear actin and myosin are critical components of the transcriptional machinery and chromatin remodeling complex.
2. Nuclear myosin controls several other cellular processes that are critical for genome integrity and the overall health of the cell.
Actin was first identified in the nucleus several decades ago, but nuclear actin function has only been actively investigated over the last couple of decades, as much of the early years post-detection were spent proving it was not an artifact or contamination(reviewed in 1).Still, many critical functions of nuclear actin have already been uncovered, while others are still under intense investigation, and new functions of nuclear actin continue to be revealed(reviewed in 1,2).
Critical functions include genome organization, regulation of nuclear shape, nuclear matrix interactions, assembly of ribonucleoprotein complexes, and gene expression(reviewed in 1, 2). Somewhat unsurprisingly, nuclear actin does not perform these functions alone; rather, it interacts with many established nuclear proteins, but also collaborates with well-known actin-binding partners like nuclear myosin to perform many of its key functions in the nucleus(reviewed in 3-5).
There are at least seven nuclear myosins that have been identified in the nucleus, but myosin IC isoform β/NM1, myosin V, and myosin VI, in particular, have been identified as regulators of key biological processes in the nucleus(reviewed in 6). These critical functions include contributing to chromatin remodeling, regulating RNA polymerases to facilitate transcription, mediating long-range directed movement of chromatin, and others, which we discuss below.
NM1, first discovered in the nucleus by the de Lanerolle lab in 20007, is highly similar to myosin IC, but has a 16-residue N-terminal extension that is critical for nuclear localization. In this study, they showed that NM1 was complexed with RNA polymerase II (RNAPII), suggesting that it may have a role in transcription. A follow-up study using a minimal in vitro transcription system showed that NM1 regulated RNAPII transcription initiation and formation of the first phosphodiester bond during transcription initiation8.
The Grummt group performed in vivo and in vitro studies revealing a role for NM1 regulation of RNA polymerase I (RNAP1)-mediated transcription9. Mechanistically, they reported that the interaction between actin and myosin, competent actin polymerization, and functional motor activity of NM1 were all required for RNAPI transcription10. A complementary study by Fomproix and Percipalle showed that nuclear myosin and actin complexed with RNAP I, and were coupled to elongating ribosomal RNA transcripts11.
The Percipalle group also identified a novel NM1 function that was independent of actin; whereby, the motor protein forms a 2-3 MDa multiprotein complex (B-WICH) with the chromatin remodeling complex, WICH,that co-localizes with RNAPI and regulates a post-initiation phase of transcription12. Follow-up studies showed that this B-WICH complex is important for recruiting histone acetyl transferase (HAT), PCAF, and the histone methyl transferase (MET), Set1/Ash2, to regulate epigenetic modifications important for chromosomal reorganization and transcription by RNAPI13 and RNAPII14.
Myosin VI also localizes to the nucleus and interacts with RNAPII to promote mRNA transcription of several genes15. In support of this, a recent study showed that nuclear myosin VI (NMVI) localized to the TNF locus in Th1 cells and regulated transcription16. Work by the Toseland group showed that NMVI interacts with NDP52, which relieved NMVI’s auto-inhibition and enabled DNA binding17. This NMVI-NDP52 complex also interacted with RNAPII to promote transcription, and depletion of either protein reduced steady-state mRNA levels.
A recent study utilized single-molecule imaging to better define NMVI’s role in the nucleus and found that it acted as a molecular anchor to hold RNAPII in high-density clusters (condensates) that were critical for spatial regulation of gene expression18. Supportive work by Jayawardana et al. used live cell structured illumination microscopy to show ligand-dependent association between androgen receptors (AR), NMVI, and nuclear actin resulted in spatial coordination at AR clusters, which were important for RNAPII transcription19.
As discussed above, NM1 interacts with the WICH complex, HATs, and METs to promote chromosomal reorganization as a mechanism to drive transcription. However, NM1 also regulates genome organization through additional mechanisms like chromosomal translocation and genome maintenance(reviewed in20, 21).
Chromosomes reside in distinct territories within the nucleus, with gene-poor chromosomes localizing near the nuclear envelope while gene-rich chromosomes inhabit a more central position(reviewed in 20). However, long-range chromosome movements between these territories have been observed, and intriguingly, several studies have shown that this type of movement is dependent on NM122,23.
Recently, Wang et al. revealed that the Hsp90 chaperone regulated motor activity of nuclear myosin to promote long-range chromosome motion across an actin matrix during gene activation[24]. Similarly, there is evidence that Lamin A/C and the Emerin protein also regulate NM1 to control the spatial positions of chromosome territories25,26.
Genome maintenance is vital for the viability of the cell. DNA damage response (DDR) is a critical mechanism cells use for genome maintenance, and we discuss NM1’s role in DDR below. DNA replication stress can also severely impact genome maintenance, and a recent study implicates a role for NMVI in the response process27. Specifically, NMVI associates with stalled replication intermediates and interacts with other proteins to prevent DNA2-mediated nucleolytic attacks.
There is growing evidence that nuclear myosin contributes to other cellular processes, many of which involve its ability to influence transcription, chromosomal organization, or migration within the nucleus. Key biological processes include DDR, metabolic reprogramming, and viral replication, which will be discussed in more detail in a future newsletter.
Collectively, these studies show that nuclear myosin’s function in genome organization and transcription can have profound effects on several cellular processes. Cytoskeleton’s actin probes have been extensively used in this field of research, check out the available products from the list below.
Myosin II protein: rabbit skeletal muscle (Cat # MY02)
Myosin protein: bovine cardiac muscle (Cat # MY03)
Actin Binding Protein Spin-Down Assay Biochem Kit: rabbit skeletal muscle actin (Cat # BK001)
Actin protein ( >99% pure): rabbit skeletal muscle (Cat # AKL99)
Actin protein (pre-formed filaments): rabbit skeletal muscle (Cat # AKF99)
Myosin - skeletal muscle S1 fragment (Cat # CS-MYS04)
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2. Szabo, A., et al., Recent advances in nuclear actin research. Nucleus, 2025. 16(1): p. 2498643.
3. Louvet, E. and P. Percipalle, Transcriptional control of gene expression by actin and myosin. Int Rev Cell Mol Biol, 2009. 272: p. 107-47.
4. de Lanerolle, P., T. Johnson, and W.A. Hofmann, Actin and myosin I in the nucleus: what next? Nat Struct Mol Biol, 2005. 12(9): p. 742-6.
5. Percipalle, P., Co-transcriptional nuclear actin dynamics. Nucleus, 2013. 4(1): p. 43-52.
6. Maly, I.V. and W.A. Hofmann, Myosins in the Nucleus. Adv Exp Med Biol, 2020. 1239: p. 199-231.
7. Pestic-Dragovich, L., et al., A myosin I isoform in the nucleus. Science, 2000. 290(5490): p. 337-41.
8. Hofmann, W.A., et al., Nuclear myosin I is necessary for the formation of the first phosphodiester bond during transcription initiation by RNA polymerase II. J Cell Biochem, 2006. 99(4): p. 1001-9.
9. Philimonenko, V.V., et al., Nuclear actin and myosin I are required for RNA polymerase I transcription. Nat Cell Biol, 2004. 6(12): p. 1165-72.
10. Ye, J., et al., Nuclear myosin I acts in concert with polymeric actin to drive RNA polymerase I transcription. Genes Dev, 2008. 22(3): p. 322-30.
11. Fomproix, N. and P. Percipalle, An actin-myosin complex on actively transcribing genes. Exp Cell Res, 2004. 294(1): p. 140-8.
12. Percipalle, P., et al., The chromatin remodelling complex WSTF-SNF2h interacts with nuclear myosin 1 and has a role in RNA polymerase I transcription. EMBO Rep, 2006. 7(5): p. 525-30.
13. Sarshad, A., et al., Nuclear myosin 1c facilitates the chromatin modifications required to activate rRNA gene transcription and cell cycle progression. PLoS Genet, 2013. 9(3): p. e1003397.
14. Almuzzaini, B., et al., Nuclear myosin 1 contributes to a chromatin landscape compatible with RNA polymerase II transcription activation. BMC Biol, 2015. 13: p. 35.
15. Vreugde, S., et al., Nuclear myosin VI enhances RNA polymerase II-dependent transcription. Mol Cell, 2006. 23(5): p. 749-55.
16. Zorca, C.E., et al., Myosin VI regulates gene pairing and transcriptional pause release in T cells. Proc Natl Acad Sci U S A, 2015. 112(13): p. E1587-93.
17. Fili, N., et al., NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nat Commun, 2017. 8(1): p. 1871.
18. Hari-Gupta, Y., et al., Myosin VI regulates the spatial organisation of mammalian transcription initiation. Nat Commun, 2022. 13(1): p. 1346.
19. Jayawardana, I.M., et al., Nuclear myosin VI cooperates with actin to promote transcriptional cluster formation at androgen receptors. J Biol Chem, 2026. 302(2): p. 111088.
20. Shahid-Fuente, I.W. and C.P. Toseland, Myosin in chromosome organisation and gene expression. Biochem Soc Trans, 2023. 51(3): p. 1023-1034.
21. Venit, T., et al., Nuclear actin and myosin in chromatin regulation and maintenance of genome integrity. Int Rev Cell Mol Biol, 2020. 355: p. 67-108.
22. Hu, Q., et al., Enhancing nuclear receptor-induced transcription requires nuclear motor and LSD1-dependent gene networking in interchromatin granules. Proc Natl Acad Sci U S A, 2008. 105(49): p. 19199-204.
23. Chuang, C.H., et al., Long-range directional movement of an interphase chromosome site. Curr Biol, 2006. 16(8): p. 825-31.
24. Wang, A., et al., Mechanism of Long-Range Chromosome Motion Triggered by Gene Activation. Dev Cell, 2020. 52(3): p. 309-320 e5.
25. Ranade, D., et al., Lamin A/C and Emerin depletion impacts chromatin organization and dynamics in the interphase nucleus. BMC Mol Cell Biol, 2019. 20(1): p. 11.
26. Pradhan, R., M.J. Nallappa, and K. Sengupta, Lamin A/C modulates spatial organization and function of the Hsp70 gene locus via nuclear myosin I. J Cell Sci, 2020. 133(4).
27. Shi, J., et al., Nuclear myosin VI maintains replication fork stability. Nat Commun, 2023. 14(1): p. 3787.
