REM

No, it’s not about the rock band.  Nor is it about sleep physiology.  Rather, this short blurb is intended to point out a recent review in Trends in Biochemical Sciences that ties together a long trickling of research extend back for many decades.

For at least 20 years, it has been known that a number of enzymes that catalyze reactons in intermediary metabolic pathways are also RNA binding proteins.  The “classical” case is that of aconitase.  This enzyme catalyzes the isomerization of citrate to isocitrate, a reaction that is part of the tricarboxylic acid cycle.  The enzyme also binds the so-called iron-responsive element in mRNAs, and in so doing regulates RNA stability and translation.  Aconitase activity and RNA binding are mutually exclusive, and the role the protein plays depends on teh iron status of the cell.

Similar RNA-binding moonlighting has since been shown for a number of other enzymes.  I won’t list them here – the review does a nice job of this.  The review also discusses the possible integration of metabolic cues with RNA homeostasis.  It doesn’t touch on a more fascinating topic – the possibility that RNA binding may be a vestige of the deep past, reflecting the possibility that, at one time, all proteins may have interacted with RNA or been involved with RNA metabolism in some way.  But the latter is a subject that better left for another review.

The abstract from the review:

‘Classic’ enzymes carry out the housekeeping functions of intermediary metabolism. The past decades have seen a steady trickle of reports of several of these enzymes ‘moonlighting’ as RNA-binding proteins. Although evidence for a physiological role for RNA binding is strong in a few individual examples, no systematic concept has been proposed for the overall phenomenon. We suggest that these diverse observations might herald the existence of currently hidden post-transcriptional regulatory networks between intermediary metabolism and gene expression based on RNA, enzyme and metabolite interactions. We briefly summarize the evidence in support of such networks and discuss how current approaches can be employed for systematic analyses and integration into our understanding of cellular biology, given the technical and conceptual advances of the ‘omics’ age.

The citation (and link, once again):

Matthias W. Hentze, Thomas Preiss, The REM phase of gene regulation, Trends in Biochemical Sciences, Volume 35, Issue 8, August 2010, Pages 423-426, ISSN 0968-0004, DOI: 10.1016/j.tibs.2010.05.009.

(http://www.sciencedirect.com/science/article/B6TCV-509WCVT-2/2/0eab8d0c2487c23c089ee35d93388b72)

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2 Responses to REM

  1. Clem Weidenbenner says:

    Art:
    This review is behind a pay wall. I could ask the corresponding author for a copy, but I’m not too committed to this subject yet. I am wondering though whether any of the dual role enzymes they discuss have been looked at thoroughly enough to know what parts of the molecule are involved in enzymatic activity (active site) vs RNA binding… and levels of sequence synteny between different taxons.

  2. Arthur Hunt says:

    Hi Clem,

    If you wish, I can forward the article.

    As for your questions, for a handful of these bifunctional enzymes, a bit of detail has been worked out and the different binding sites have been delineated. cis-aconitase is the best example, and the review provides a nice summary. Google or Pubmed will also fetch an interesting story. (The short version for this enzyme – RNA binding and enzyme activity are regulated by an iron-sulfur cluster, and the two activities are mutually exclusive.)

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