nanos and pumilio Are Essential for Dendrite Morphogenesis in Drosophila Peripheral Neurons

Yan, Bing; Petritsch, Claudia; Clark, Ira E.; Gavis, Elizabeth R.; Jan, Yuh Nung

doi:10.1016/j.cub.2004.01.052

Cited by 165 publications

(101 citation statements)

References 30 publications

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“…Thus, it seems possible that Smaug 1 molecules located at post-synaptic sites specifically sequester SRE-containing transcripts in granules, where translation is suppressed. More importantly, a growing number of RNA-binding proteins thought to be involved in the local regulation of gene expression are present in dendrites and post-synaptic sites forming granules (11,26,29,(42)(43)(44)(45). Relevantly, some of them, namely Staufen, SMN, fragile X mental retardation protein, and ELAV family members, are also found, under certain conditions, in larger accretions eventually identified as stress granules in a number of cases (20, 46 -48).…”

Section: Discussionmentioning

confidence: 99%

Mammalian Smaug Is a Translational Repressor That Forms Cytoplasmic Foci Similar to Stress Granules

Báez

Boccaccio

2005

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Mammalian Smaug Is a Translational Repressor That Forms Cytoplasmic Foci Similar to Stress Granules

Báez

Boccaccio

2005

Journal of Biological Chemistry

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“…Such recognition may be directed toward unstructured RNA requiring discrimination of RNA sequences, folded RNA motifs, or some combination of sequence and structural specificity (1). Members of the PUF 2 protein family (named after Drosophila Pumilio and Caenorhabditis elegans fem-3 mRNA-binding factor (FBF)) are sequence-specific RNA-binding proteins that regulate networks of mRNAs encoding proteins of related function (2)(3)(4)(5)(6)(7). PUF proteins generally recognize the 3Ј-UTR of their target mRNAs to control the mRNA stability and translation (2)(3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Specific and Modular Binding Code for Cytosine Recognition in Pumilio/FBF (PUF) RNA-binding Domains

Dong

Wang

Cassidy-Amstutz

et al. 2011

Journal of Biological Chemistry

140

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Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for cytosine are unknown. Here we report identification of a cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and the cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.The specific interaction of RNA and protein plays vital roles in RNA regulation including splicing, localization, translation, and degradation. Such recognition may be directed toward unstructured RNA requiring discrimination of RNA sequences, folded RNA motifs, or some combination of sequence and structural specificity (1). Members of the PUF 2 protein family (named after Drosophila Pumilio and Caenorhabditis elegans fem-3 mRNA-binding factor (FBF)) are sequence-specific RNA-binding proteins that regulate networks of mRNAs encoding proteins of related function (2-7). PUF proteins generally recognize the 3Ј-UTR of their target mRNAs to control the mRNA stability and translation (2-7).The RNA-binding domain of PUF proteins, known as the Pumilio homology domain (PUM-HD) or PUF domain, can bind to unstructured RNA sequences in a distinct fashion. The PUF domain of human Pumilio 1 contains eight PUM repeats, each containing three ␣-helices packed together in a curved structure (8 -10). RNA is bound as an extended strand to the concave surface of the PUF domain with the bases contacted by protein side chains. In general, each PUM repeat recognizes a single RNA base through the second helix (␣2) in an antiparallel arrangement, i.e. nucleotides 1-8 are recognized by PUF repeats 8 -1, respectively. The ␣2 helices of PUM repeats contain a 5-residue sequence, designated here as 12XX5, where the side chain at position 2 stacks with the recognized base and the side chains at positions 1 and 5 recognize the edge of the base (8, 11) (see Fig. 1A). Specific residues at these positions direct the base recognition properties of the repeat. This PUF-RNA recognition code makes it possible to modify a PUM repeat to bind a particular RNA base, producing a designed PUF domain that specifically recognizes a given 8-nucleotide RNA target. Such de novo designed RNA binders have been used to track RNA local...

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“…A common function of Puf proteins is regulating germ-line stem cell development, perhaps their ancestral function (14). Drosophila melanogaster Pumilio (DmPUM), the founding member of the Puf family, was noted first for regulating abdominal development by repressing the translation of maternal hunchback (hb mat ) mRNA (15-17) and is also important for regulating germ-line stem cell development (18)(19)(20), anterior patterning (21), and neuronal function (22)(23)(24)(25). DmPUM represses hb mat expression by binding to tandem sequence motifs, Nanos response elements (NREs), in the hb mat 3Ј UTR (26).…”

mentioning

confidence: 99%

Engineering RNA sequence specificity of Pumilio repeats

Cheong

Hall

2006

Proc. Natl. Acad. Sci. U.S.A.

214

255

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Puf proteins bind RNA sequence specifically and regulate translation and stability of target mRNAs. A ''code'' for RNA recognition has been deduced from crystal structures of the Puf protein, human Pumilio1, where each of eight repeats binds an RNA base via a combination of three side chains at conserved positions. Here, we report the creation of seven soluble mutant proteins with predictably altered sequence specificity, including one that binds tightly to adenosine-uracil-rich element RNA. These data show that Pumilio1 can be used as a scaffold to engineer RNA-binding proteins with designed sequence specificity.protein design ͉ Puf proteins ͉ protein-RNA interaction ͉ adenosine-uracil-rich elements S pecific nucleotide sequences in mRNA molecules, often in noncoding sequences, regulate processes such as turnover, translation, localization, and splicing that are necessary for producing correct protein products in the right amounts at the right times and places. Proteins that bind to the specific RNA sequences often direct these posttranscriptional regulatory events, which are important during both embryonic development and cellular homeostasis. Two examples are the regulatory roles of sequences in the 3Ј UTRs of mRNAs and near alternative splice sites in pre-mRNAs. Expression of TNF␣ is regulated by an adenosine-uracil-rich element (ARE) in the 3Ј UTR of its mRNA, a common motif that confers instability on the message (1, 2). This sequence is recognized by the tristetraprolin (TTP) family of proteins, which initiates degradation of the AREcontaining mRNA (3). Overproduction of TNF␣, as in the absence of TTP, results in inflammatory disorders such as rheumatoid arthritis, cachexia, and autoimmunity (4). Alternative splicing events are directed by specific exon-intron junction motifs and positive and negative regulatory sequences within the exons or introns. Mutations in these sequences can result in splicing defects that lead to diseases such as cancer, spinal muscular atrophy, and cystic fibrosis (5).Because of the importance of RNA regulatory sequences in human health and disease, RNA-binding proteins with designed specificity could be important as tools for understanding processes directed by specific RNA sequences or perhaps as therapeutic agents. For example, an RNA-binding protein with specificity for a splicing regulatory sequence could induce a preferred alternatively spliced product by blocking an alternative splicing event. Or an RNA-binding protein with specificity for a particular RNA could be tracked by fusing the RNA-binding domain with a green fluorescent protein partner. Other work on designing RNA-binding proteins has focused on folded RNA targets such as the HIV-1 Rev response element RNA by using zinc fingers or arginine-rich motif peptides and relied generally on screening of proteins with selected randomized positions or building a chimeric molecule (6-12). Our previous studies of the Puf family protein, human Pumilio1, a sequence-specific RNAbinding protein, suggested that it could be used ...

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nanos and pumilio Are Essential for Dendrite Morphogenesis in Drosophila Peripheral Neurons

Cited by 165 publications

References 30 publications

Mammalian Smaug Is a Translational Repressor That Forms Cytoplasmic Foci Similar to Stress Granules

Mammalian Smaug Is a Translational Repressor That Forms Cytoplasmic Foci Similar to Stress Granules

Specific and Modular Binding Code for Cytosine Recognition in Pumilio/FBF (PUF) RNA-binding Domains

Engineering RNA sequence specificity of Pumilio repeats

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