Roles of Puf proteins in mRNA degradation and translation

Miller, Melanie A.; Olivas, Wendy M.

doi:10.1002/wrna.69

Cited by 141 publications

(155 citation statements)

References 124 publications

(372 reference statements)

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…The P values were evaluated via one-way ANOVAs. , presynaptic CS+US signals (blue), but not CS alone or US alone (gray), an CREB-independent mechanism relieves the translational block of RNA granules, which involves (i) STAUFEN detachment (38,41), (ii) FMR and PUMILIO dephosphorylations (38,42,43), and (iii) ORB phosphorylation by activated CaMKII, leading to the poly-A tail elongation (4)(5)(6). Consequently, these events recruit additional ribosomes to up-regulate mRNA translation of LTM-related proteins (42), which eventually lead to an enhanced response to the CS+.…”

Section: Methodsmentioning

confidence: 99%

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

Pai

Chen

Lin

et al. 2013

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

121

135

View full text Add to dashboard Cite

Memory is initially labile and gradually consolidated over time through new protein synthesis into a long-lasting stable form. Studies of odor-shock associative learning in Drosophila have established the mushroom body (MB) as a key brain structure involved in olfactory long-term memory (LTM) formation. Exactly how early neural activity encoded in thousands of MB neurons is consolidated into protein-synthesis-dependent LTM remains unclear. Here, several independent lines of evidence indicate that changes in two MB vertical lobe V3 (MB-V3) extrinsic neurons are required and contribute to an extended neural network involved in olfactory LTM: (i) inhibiting protein synthesis in MB-V3 neurons impairs LTM; (ii) MB-V3 neurons show enhanced neural activity after spaced but not massed training; (iii) MB-V3 dendrites, synapsing with hundreds of MB α/β neurons, exhibit dramatic structural plasticity after removal of olfactory inputs; (iv) neurotransmission from MB-V3 neurons is necessary for LTM retrieval; and (v) RNAi-mediated downregulation of oo18 RNA-binding protein (involved in local regulation of protein translation) in MB-V3 neurons impairs LTM. Our results suggest a model of long-term memory formation that includes a systems-level consolidation process, wherein an early, labile olfactory memory represented by neural activity in a sparse subset of MB neurons is converted into a stable LTM through protein synthesis in dendrites of MB-V3 neurons synapsed onto MB α lobes.L ong-term memory (LTM) and long-term synaptic plasticity require de novo protein synthesis, which is regulated at transcriptional and/or translational levels in a synapse-specific manner (1-3). Synapse-specific plasticity during LTM formation in some contexts may involve local regulation of protein translation by a family of RNA-binding proteins, the cytoplasmic polyadenylation element-binding proteins (CPEBs) (2). Neuronal CPEBs have two conformational states. The inactive state predominates at low levels of CPEB expression and represses translation from nascent mRNAs. The active state is achieved either via a self-perpetuating prion-like state when expression levels surpass a threshold or via Ca 2+ /calmoduline-dependent protein kinase II (CaMKII)-mediated phosphorylation, and translation is initiated by elongation of an mRNA's poly-A tail (4-6). In other species, CPEB1 has been shown to contribute to long-term facilitation or potentiation (5, 7). In Drosophila, oo18 RNA-binding protein 2 (ORB2) appears required for long-term memory formation after courtship conditioning (8, 9). Any role for ORB in fruit fly memory formation, however, remains unclear.Drosophila can learn to associate an odor (conditioned stimulus, CS) with foot-shock punishment (unconditioned stimulus, US). This odor-shock association initially is labile, lasting for only about a day after one training session. With repetitive, spaced training (ST) sessions (rest intervals between each session), a protein synthesis-dependent, LTM is formed. With repetitive, massed training (MT) ses...

show abstract

Section: Methodsmentioning

confidence: 99%

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

Pai

Chen

Lin

et al. 2013

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

121

135

View full text Add to dashboard Cite

show abstract

“…Subtle degeneracy was observed at nucleotide position 4 in the sequences of APUM2 and APUM6, whereas a higher degree of degeneracy was observed at position 5 in these sequences. Degeneracy at position 5 is common for many other PUF protein targets (23). APUM12 deviated from the classical one repeat-one nucleotide pattern for PUF binding, because it showed an insertion of an additional uracil near the 3Ј end of its consensus sequence when compared with the target sequences A Unique PUF RNA Target Sequence DECEMBER 11, 2015 • VOLUME 290 • NUMBER 50…”

Section: Prediction Of Puf Repeats In the Selected Apum Proteins-mentioning

confidence: 99%

A Nucleolar PUF RNA-binding Protein with Specificity for a Unique RNA Sequence

Zhang

Muench

2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

PUF proteins are a conserved group of sequence specific RNA-binding proteins that bind to RNA in a modular fashion. The RNA-binding domain of PUF proteins typically consists of eight clustered Puf repeats. Plant genomes code for large families of PUF proteins that show significant variability in their predicted Puf repeat number, organization, and amino acid sequence. Here we sought to determine whether the observed variability in the RNA-binding domains of four plant PUFs results in a preference for nonclassical PUF RNA target sequences. We report the identification of a novel RNA binding sequence for a nucleolar Arabidopsis PUF protein that contains an atypical RNA-binding domain. The Arabidopsis PUM23 (APUM23) binding sequence was 10 nucleotides in length, contained a centrally located UUGA core element, and had a preferred cytosine at nucleotide position 8. These RNA sequence characteristics differ from those of other PUF proteins, because all natural PUFs studied to date bind to RNAs that contain a conserved UGU sequence at their 5 end and lack specificity for cytosine. Gel mobility shift assays validated the identity of the APUM23 binding sequence and supported the location of 3 of the 10 predicted Puf repeats in APUM23, including the cytosine-binding repeat. The preferred 10-nucleotide sequence bound by APUM23 is present within the 18S rRNA sequence, supporting the known role of APUM23 in 18S rRNA maturation. This work also reveals that APUM23, an ortholog of yeast Nop9, could provide an advanced structural backbone for Puf repeat engineering and target-specific regulation of cellular RNAs.

show abstract

“…PUF proteins repress target mRNA expression by inhibiting translation and/or inducing mRNA degradation (Miller and Olivas 2011), but the mechanisms and cofactors involved remain to be fully elucidated. Our recent results revealed that human and Drosophila PUFs possess multiple domains that contribute to repression .…”

Section: Introductionmentioning

confidence: 99%

The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation

Weidmann

Raynard

Blewett

et al. 2014

RNA

117

View full text Add to dashboard Cite

PUF proteins are potent repressors that serve important roles in stem cell maintenance, neurological processes, and embryonic development. These functions are driven by PUF protein recognition of specific binding sites within the 3 ′ untranslated regions of target mRNAs. In this study, we investigated mechanisms of repression by the founding PUF, Drosophila Pumilio, and its human orthologs. Here, we evaluated a previously proposed model wherein the Pumilio RNA binding domain (RBD) binds Argonaute, which in turn blocks the translational activity of the eukaryotic elongation factor 1A. Surprisingly, we found that Argonautes are not necessary for repression elicited by Drosophila and human PUFs in vivo. A second model proposed that the RBD of Pumilio represses by recruiting deadenylases to shorten the mRNA's polyadenosine tail. Indeed, the RBD binds to the Pop2 deadenylase and accelerates deadenylation; however, this activity is not crucial for regulation. Rather, we determined that the poly(A) is necessary for repression by the RBD. Our results reveal that poly(A)-dependent repression by the RBD requires the poly(A) binding protein, pAbp. Furthermore, we show that repression by the human PUM2 RBD requires the pAbp ortholog, PABPC1. Pumilio associates with pAbp but does not disrupt binding of pAbp to the mRNA. Taken together, our data support a model wherein the Pumilio RBD antagonizes the ability of pAbp to promote translation. Thus, the conserved function of the PUF RBD is to bind specific mRNAs, antagonize pAbp function, and promote deadenylation.

show abstract

Roles of Puf proteins in mRNA degradation and translation

Cited by 141 publications

References 124 publications

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

A Nucleolar PUF RNA-binding Protein with Specificity for a Unique RNA Sequence

The RNA binding domain of Pumilio antagonizes poly-adenosine binding protein and accelerates deadenylation

Contact Info

Product

Resources

About