The first solid evidence for a link between actin and gene transcription came from experiments in which actin antibodies or actin-binding proteins were injected into the germinal vesicle of salamander oocytes, resulting in a retraction of nascent RNA on the lateral loops of the meiotic (“lamp-brush”) chromosomes (Scheer et al., 1984
). These investigators also reported the formation of a perichromosomal meshwork of filaments when transcription was inhibited by actinomycin and suggested that these filaments were actin, based on their observed fragmentation by the F-actin-severing protein fragmin. Although the Scheer et al
. article had a degree of impact, it did not generate a following in the eukaryotic transcription field. Ironically, at just the same time there was a beacon from a major transcription laboratory hinting at actin as an important factor (Egly et al., 1984
), but this finding, too, was also largely ignored. It is sobering to note that virtually all of the experimental systems and biochemical knowledge of transcription that have very recently been used to definitively implicate actin were available in 1984. As often happens, it was a paradigm shift that was needed, not the development of new technology. Although a number of key advances in the nuclear actin field occurred after 1984 (Olave et al., 2002
; Pederson and Aebi, 2002
), it was 17 years before the issue was investigated in further depth. This time, the concept took hold.
In 2001, actin was found to be associated with the Balbiani ring 2 nascent pre-mRNA in Chironomus
salivary gland polytene chromosomes (Percipalle et al., 2001
), and soon thereafter the same group reported that actin also forms complexes with the pre-mRNA binding hnRNP A- and B-type proteins (Percipalle et al., 2002
). Subsequently this group provided evidence that the role of actin in stimulating or sustaining pre-mRNA transcription requires its interaction with heterogeneous nuclear ribonucleoprotein (hnRNP) proteins (Percipalle et al., 2003
). In short order, another study strongly implicated nuclear actin in RNA polymerase II transcription in growing mammalian cells (Hofmann et al., 2004
), indicating that a transcriptional role of actin is not limited to the meiosis-arrested amphibian oocyte (Scheer et al., 1984
) or the insect larval polytene nucleus (Percipalle et al
; Percipalle et al., 2003
), however implausible that hypothesis might have been.
There have been numerous reports linking nuclear actin to the phenomenon of chromatin remodeling (reviewed in Olave et al., 2002
), although there has not been uniform acceptance of this conclusion. A recent investigation in the aforementioned Chironomus
system has now added further evidence for a connection among nuclear actin, chromatin remodeling, and RNA polymerase II transcription (Sjölinder et al., 2005
.) In this study, it was found a peptide that inhibits the actin-nascent pre-mRNP association was counteracted by trichostatin A, which inhibits histone deacetylation. Additional experiments revealed that both actin and the pre-mRNP protein hrp65 are complexed in situ with the histone H3-specific acetyltransferase p2D10 and that disruption of the actin–hrp65 interaction causes release of p2D10 from Pol II-transcribing genes coincident with reduced H3 acetylation and diminished transcription. These new findings (Sjölinder et al., 2005
) considerably bolster the notion of a link among nuclear actin, chromatin remodeling, and Pol II transcription—the connection between the latter two phenomena already well established.