Title:
Eukaryotic gene expression: the function of actin and actin-associated proteins in transcription
Abstract
In the cell nucleus, actin is an important regulator of gene expression, found as component of ATP-dependent chromatin remodelling complexes, ribonucleoprotein particles (RNP) and more recently, associated with all three eukaryotic RNA polymerases. A lot of effort is currently placed on deciphering the molecular mechanisms underlying the function of actin in gene activation, through the identification of nuclear actin-associated proteins.
This lecture will focus on two ongoing studies in my laboratory, to clarify how actin specifically functions in transcription.
Actin in transcription of protein-coding genes
We have recently discovered that actin is required to turn on transcription of protein-coding genes associated with the active RNA polymerase II, in complex with the ribonucleoprotein hnRNP U (Kukalev et al., 2005). In this study, we also found that actin binds hnRNP U through a short and conserved (from insect to mammals) amino acid sequence motif. Given that hnRNP U and actin are respectively coupled to histone acetyl transferase activities (p300/CBP) and chromatin remodelling complexes, we propose a model in which the actin-hnRNP U complex activates transcription by recruiting chromatin modifying components.
Actin in ribosomal DNA (rDNA) transcription
After the discovery of a nuclear form of myosin 1 (NM1) and its direct involvement in transcription initiation of protein-coding genes, it seemed possible that actin and myosin could perform a concerted general role in transcription. In support of this possibility, we found that actin and NM1 are on actively transcribing ribosomal genes bound to the largest RNA polymerase I subunit (Fomproix and Percipalle, 2004).
We recently discovered that NM1 is a component of a multiprotein assembly, containing the chromatin remodelling complex WSTF-ISWI, which activates rDNA transcription (Percipalle et al., 2005). Considering the very dynamic interaction between actin and NM1, we suggest that they activate and maintain productive rDNA transcription as molecular switches, recruiting RNA polymerase I co-activators on ribosomal genes (Percipalle et al., 2005).
In conclusion, our data suggest a key role for actin in transcription. An interesting scenario is that transcription of all RNA polymerases is facilitated by actin-based molecular switches in which the polymerase-associated actin binds to specific adaptors (such as hnRNP U and NM1) to recruit transcription co-activators.
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