The long journey of actin and actin-associated proteins from genes to polysomes

Abstract

During gene expression, multiple regulatory steps make sure that alterations of chromatin structure are synchronized with RNA synthesis, co-transcriptional assembly of ribonucleoprotein complexes, transport to the cytoplasm and localized translation. These events are controlled by large multiprotein complexes commonly referred to as molecular machines, which are specialized and at the same time display a highly dynamic protein composition. The crosstalk between these molecular machines is essential for efficient RNA biogenesis. Actin has been recently proposed to be an important factor throughout the entire RNA biogenesis pathway as a component of chromatin remodeling complexes, associated with all eukaryotic RNA polymerases as well as precursor and mature ribonucleoprotein complexes. The aim of this review is to present evidence on the involvement of actin and actin-associated proteins in RNA biogenesis and propose integrative models supporting the view that actin facilitates coordination of the different steps in gene expression.

Fig. 1

The above diagram summarizes the involvement of actin in nuclear function. Actin has been shown to be a component of chromatin remodeling complexes, to be associated with eukaryotic RNA polymerases and to be incorporated in RNP complexes. Evidence of active nucleocytoplasmic transport also suggests a functional crosstalk between nuclear and cytoplasmic actin

Fig. 2

Actin accompanies mRNA transcripts from gene to polysomes. Actin cooperates with hnRNP U during the elongation of nascent pre-mRNA transcripts for recruitment of the HAT PCAF to active genes. Actin is further incorporated in pre-mRNPs/mRNPs in transit to the nuclear pore complex. Finally, there is evidence that actin follows mRNPs to the cytoplasm and may be required for mRNA export. However, at this stage there is no direct evidence that the actin-associated RNP is involved in mRNA localization on the actin cytoskeleton

Fig. 3

The role of actin and NM1 in rRNA biogenesis. a Schematic representation of the “molecular switch” model where the dynamic actin–NM1 interaction has been recently proposed to mediate recruitment of the chromatin remodeling B-WICH to active rRNA genes for efficient pre-rRNA elongation [20, 51, 53]. b Emerging evidence suggests that the B-WICH complex is added to nascent pre-rRNP complexes to facilitate rRNA remodeling [81]

Fig. 4

Proposed model for the involvement of NM1 in post-transcriptional control of rRNA biogenesis. After being incorporated in nascent pre-rRNA complexes, NM1 is likely to accompany the rRNA transcripts through processing, assembly into pre-ribosomal subunits and transport to the nuclear pore complex. Given its role in RNA polymerase I transcription, it is possible that NM1 links transcription with processing and transport by implementing quality control mechanisms for efficient rRNA biogenesis

Fig. 5

An integrative model illustrating how the different polymerization states of nuclear actin may affect nuclear function. N-WASP and ARP2/3 are likely to cooperate in order to stabilize polymeric actin during transcription elongation, while the monomeric actin pool may be continuously replenished by the combined action of cofilin and profilin. In this context the role of nuclear GTPases has not been investigated yet. However, other mechanisms should also be considered in the modulation of the fine balance between monomeric and polymeric nuclear actin, given for instance genetic evidence that formins and formin-like proteins are present in the cell nucleus