Ssu72 Introduction

The Ssu72 RNA polymerase II CTD phosphatase homolog is a protein from Drosophila melanogaster that shares a high level of sequence similarity with the human Ssu72 protein - the function of which has been characterised to some degree in the literature and a number of putative homologs identified across a broad range of species. While there are fewer than 10 papers in PubMed that reference the human protein, it is useful to give at least a cursory examination of some of that information at this point to provide context for a discussion of the speculative function of the drosophila protein; particularly given that it shares a 60.21% sequence identity with the human Ssu72 protein, and that there are no gaps in the alignment produced after running a BLAST (See figure 1). This preliminary sequence alignment is suggestive that, on the face of it, there may be, at the least, a broad similarity in function that can be inferred from the human protein by virtue of Ssu72's strong conservation across evolution.

On a preliminary reading of the literature, which is more thoroughly considered in the 'function' section of the discussion, it is clear that the human Ssu72 protein functions as a protein phosphatase in vivo. Protein phosphatases, broadly speaking and regardless of the substrate that they act on, perform a role which is the reverse of that performed by phosphorylases and kinases - that is to say, protein phosphatases bring about the removal of a phosphate group (dephosphorylation) from their substrate (Barford, 1996). While there are different types of such protein phosphatases, which are classified according to their substrate, they each operate via equivalent biochemical reactions. Therefore, human Ssu72, and almost certainly too the Drosophila protein, exert their activity by catalysing the hydrolysis of phosphoric acid. The effect that this has in vivo has been experimentally demonstrated to be dephosphorylation of the C-terminal domain of RNA Polymerase II (Krishnamurthy et al., 2004). Therefore, based on this interaction and the fact that Ssu72 null mutations confer lethality (Meinhardt, Silberzahn, & Cramer, 2003), it is clear that the Ssu72 family of proteins potentially play a fundamental role in the regulation of transcription, by at the very least modulating the level of phosphorylation of RNA Polymerase II.

References

Barford, D. Molecular mechanisms of the protein serine/threonine phosphatases, (1996) Trends Bioch Sci, 21(11), p. 407.

Krishnamurthy, S., He, X., Reyes-Reyes, M., Moore, C., and Hampsey, M. (2004) Ssu72 Is an RNA Polymerase II CTD Phosphatase. Molecular Cell 14(3), pp. 387-394.

Meinhart, A., Silberzahn, T., and Cramer, P. (2003) The mRNA Transcription/Processing Factor Ssu72 Is a Potential Tyrosine Phosphatase J. Biol. Chem., Vol. 278, Issue 18, 15917-15921.

Abstract | Introduction | Results | Discussion | Method | References