PROSITE documentation PDOC50302

Pumilio RNA-binding repeat and homology domain profiles

Members of the Pumilio family of proteins (Puf) regulate translation and mRNA stability in a wide variety of eukaryotic organisms including mammals, flies, worms, slime mold, and yeast [1]. Pumilio family members are characterized by the presence of eight tandem copies of an imperfectly repeated 36 amino acids sequence motif, the Pumilio repeat, surrounded by a short N- and C-terminal conserved region. The eight repeats and the N- and C-terminal regions form the Pumilio homology domain (PUM-HD). The PUM-HD domain is a sequence-specific RNA binding domain. Several Puf members have been shown to bind specific RNA sequences mainly found in the 3' UTR of mRNA and repress their translation [2]. Frequently, Puf proteins function asymmetrically to create protein gradients, thus causing asymmetric cell division and regulating cell fate specification [3].

Crystal structure of Pumilio repeats has been solved (see <PDB:1IB2>) [4]. The PUM repeat with the N- and C-terminal regions pack together to form a right-handed superhelix that approximates a half doughnut structurally similar to the Armadillo (ARM) repeat proteins (see <PDOC50176>), β-catenin and karyopherin α. The RNA binds the concave surface of the molecule, where each of the protein's eight repeats makes contacts with a different RNA base via three amino acid side chains at conserved positions [5].

Some of the proteins known to contain Pumilio repeats are listed below:

• Drosophila Pumilio protein. It is a sequence-specific RNA-binding protein that binds to the Nanos Response Element (NRE), a 16 bp sequence in the hunchback mRNA 3'UTR.
• Xenopus Pumilio. It also interacts with a Nanos protein, Xcat-2.
• Human PUM1 and PUM2. They have an important role in cell development, fate specification and differentiation.
• Yeast PUF3 protein. It is a transcript-specific regulator of mRNA degradation and binds the 3'UTR of the COX17 protein.
• Dictyostelium PufA protein. It represses expression of protein kinase A mRNA, and appears to be a key developmental regulator in that organism.
• Caenorhabditis elegans fbf-1 and fbf-2. They mediate the sperm/oocyte switch in hermaphrodites by binding the 3' UTR of the fem-3 mRNA and repressing its expression.

Two profiles were developed for this conserved region, the first one picks up pumilio repeat units while the second one detects the whole PUM-HD domain.