DDX5/p68 RNA helicase is expressed in dividing cells of different vertebrates. Transcription of p68 RNA helicase gene generates a single mRNA precusor with 13 exons and 12 introns. Alternative splicing produces two mRNA transcripts, 2.3 kb and 4.4 kb (Rössler et al., 2000). The 2.3 kb mRNA transcript codes full length p68, while no translational product from the 4.4 kb mRNA transcript is detected in cellular and tissue extracts (Rössler et al., 2000).

Size of p68; 614 amino acids, 69 kDa.

Expressed in almost all tissue types. Its expression is increased in cancer cells.

Dominately localized in the cell nucleus. It is also found in the cytoplasm in various physiological conditions. p68 is a nucleocytoplasm shuttling protein (Wang et al., 2009).

Pre-mRNA splicing. The protein was demonstrated to associate with spliceosome by mass-spectroscopy and an RNA-protein crosslinking analyses (Hartmuth et al., 2002; Liu et al., 1997; Neubauer et al., 1998). p68 is functionally involved in assemble of the splicesome by mediating the U1 snRNP and the 5ss interaction (Liu, 2002). p68 RNA helicase is also shown to regulate the splice site selection in the alternative splicing of several growth related genes, such as c-H-ras and tau (Kar et al., 2011; Guil et al., 2003).

Transcriptional regulation. The protein is shown to involve in transcriptional regulation by different mechanism of actions dependent on each individual regulated gene and biological processes (Stevenson et al., 1998; Endoh et al., 1999; Yang et al., 2005; Kahlina et al., 2004; Wei and Hu, 2001; Warner et al., 2004). p68 may regulate gene transcription by direct interaction with transcription factors or activators, such as p53, ERalpha (Endoh et al., 1999; Bates et al., 2005), or by mediating chromatin remodeling, such as modulating chromatin remodeling complex (Carter et al., 2010).

Epithelial-Mesenchymal-Transition (EMT). p68 becomes phosphorylated at Y593 upon growth factor stimulation by c-Abl. The tyrosine phosphorylation of p68 mediates growth factor stimulated Epithelial-Mesenchymal-Transition (EMT) (Yang et al., 2006).

Other functions. (1) p68 RNA helicase is shown to unwind the human let-7 microRNA precursor duplex. The protein is required for let-7-directed silencing of gene expression (Salzman et al., 2007). p68 is an indispensible part of Drosha complex. Its activity is required for primary miRNA and rRNA processing (Fukuda et al., 2007). (2) It is also demonstrated that the RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation (Caretti et al., 2006). (3) Phosphorylation of p68 at Thr residues mediates cell apoptosis (Yang et al., 2007).

Yeast DBP2.

Very few mutations of p68 gene were reported. A recent study shows that a S480A mutation in hepatic stellate cells is associated with hepatic fibrosis (Guo et al., 2010).