scholarly journals Distinct Expression Patterns Predict Differential Roles of the miRNA-Binding Proteins, Lin28 and Lin28b, in the Mouse Testis: Studies During Postnatal Development and in a Model of Hypogonadotropic Hypogonadism

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1321-1336 ◽  
Author(s):  
Francisco Gaytan ◽  
Susana Sangiao-Alvarellos ◽  
María Manfredi-Lozano ◽  
David García-Galiano ◽  
Francisco Ruiz-Pino ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Binding Proteins ◽  
Rna Binding ◽  
Hypogonadotropic Hypogonadism ◽  
Expression Patterns ◽  
Mouse Testis ◽  
Null Mouse ◽  
Cellular Distribution ◽  
Protein Distribution ◽  
Postnatal Maturation

Abstract Lin28 (also termed Lin28a) and Lin28b are related RNA-binding proteins, involved in the control of microRNA synthesis, especially of the let-7 family, with putative functions in early (embryo) development. However, their roles during postnatal maturation remain ill defined. Despite the general assumption that Lin28 and Lin28b share similar targets and functions, conclusive demonstration of such redundancy is still missing. In addition, recent observations suggest a role of Lin28 proteins in mammalian reproduction, which is yet to be defined. We document herein the patterns of RNA expression and protein distribution of Lin28 and Lin28b in mouse testis during postnatal development and in a model of hypogonadotropic hypogonadism as a result of inactivation of the kisspeptin receptor, Gpr54. Lin28 and Lin28b mRNAs were expressed in mouse testis across postnatal maturation, but their levels disparately varied between neonatal and pubertal periods, with peak Lin28 levels in infantile testes and sustained elevation of Lin28b mRNA in young adult male gonads, where relative levels of let-7a and let-7b miRNAs were significantly suppressed. In addition, Lin28 peptides displayed totally different patterns of cellular distribution in mouse testis: Lin28 was located in undifferentiated and type-A1 spermatogonia, whereas Lin28b was confined to spermatids and interstitial Leydig cells. These profiles were perturbed in Gpr54 null mouse testis, which showed preserved but irregular Lin28 signal and absence of Lin28b peptide, which was rescued by administration of gonadotropins, mainly hCG (as super-agonist of LH). In addition, increased relative levels of Lin28, but not Lin28b, mRNA and of let-7a/let-7b miRNAs were observed in Gpr54 KO mouse testes. Altogether, our data are the first to document the divergent patterns of cellular distribution and mRNA expression of Lin28 and Lin28b in the mouse testis along postnatal maturation and their alteration in a model of congenital hypogonadotropic hypogonadism. Our findings suggest distinct functional roles of these two related, but not overlapping, miRNA-binding proteins in the male gonad.

scholarly journals Translational Control of Cytochrome c by RNA-Binding Proteins TIA-1 and HuR

2006 ◽  
Vol 26 (8) ◽  
pp. 3295-3307 ◽  
Author(s):  
Tomoko Kawai ◽  
Ashish Lal ◽  
Xiaoling Yang ◽  
Stefanie Galban ◽  
Krystyna Mazan-Mamczarz ◽  
...  
Keyword(s):  
Er Stress ◽  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Coding Region ◽  
Translation Rate ◽  
Translational Repressor

ABSTRACT Stresses affecting the endoplasmic reticulum (ER) globally modulate gene expression patterns by altering posttranscriptional processes such as translation. Here, we use tunicamycin (Tn) to investigate ER stress-triggered changes in the translation of cytochrome c, a pivotal regulator of apoptosis. We identified two RNA-binding proteins that associate with its ∼900-bp-long, adenine- and uridine-rich 3′ untranslated region (UTR): HuR, which displayed affinity for several regions of the cytochrome c 3′UTR, and T-cell-restricted intracellular antigen 1 (TIA-1), which preferentially bound the segment proximal to the coding region. HuR did not appear to influence the cytochrome c mRNA levels but instead promoted cytochrome c translation, as HuR silencing greatly diminished the levels of nascent cytochrome c protein. By contrast, TIA-1 functioned as a translational repressor of cytochrome c, with interventions to silence TIA-1 dramatically increasing cytochrome c translation. Following treatment with Tn, HuR binding to cytochrome c mRNA decreased, and both the presence of cytochrome c mRNA within actively translating polysomes and the rate of cytochrome c translation declined. Taken together, our data suggest that the translation rate of cytochrome c is determined by the opposing influences of HuR and TIA-1 upon the cytochrome c mRNA. Under unstressed conditions, cytochrome c mRNA is actively translated, but in response to ER stress agents, both HuR and TIA-1 contribute to lowering its biosynthesis rate. We propose that HuR and TIA-1 function coordinately to maintain precise levels of cytochrome c production under unstimulated conditions and to modify cytochrome c translation when damaged cells are faced with molecular decisions to follow a prosurvival or a prodeath path.

scholarly journals FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Raeann Goering ◽  
Laura I Hudish ◽  
Bryan B Guzman ◽  
Nisha Raj ◽  
Gary J Bassell ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Fragile X ◽  
Rna Localization ◽  
Null Mouse ◽  
Rna Sequences ◽  
Rna Molecules ◽  
G Quadruplex

The sorting of RNA molecules to subcellular locations facilitates the activity of spatially restricted processes. We have analyzed subcellular transcriptomes of FMRP-null mouse neuronal cells to identify transcripts that depend on FMRP for efficient transport to neurites. We found that these transcripts contain an enrichment of G-quadruplex sequences in their 3′ UTRs, suggesting that FMRP recognizes them to promote RNA localization. We observed similar results in neurons derived from Fragile X Syndrome patients. We identified the RGG domain of FMRP as important for binding G-quadruplexes and the transport of G-quadruplex-containing transcripts. Finally, we found that the translation and localization targets of FMRP were distinct and that an FMRP mutant that is unable to bind ribosomes still promoted localization of G-quadruplex-containing messages. This suggests that these two regulatory modes of FMRP may be functionally separated. These results provide a framework for the elucidation of similar mechanisms governed by other RNA-binding proteins.

scholarly journals Changes in Hypothalamic Expression of the Lin28/let-7 System and Related MicroRNAs During Postnatal Maturation and After Experimental Manipulations of Puberty

Endocrinology ◽  
2013 ◽  
Vol 154 (2) ◽  
pp. 942-955 ◽  
Author(s):  
S. Sangiao-Alvarellos ◽  
M. Manfredi-Lozano ◽  
F. Ruiz-Pino ◽  
V.M. Navarro ◽  
M.A. Sánchez-Garrido ◽  
...  
Keyword(s):  
Rna Binding ◽  
Expression Profiles ◽  
Association Studies ◽  
Expression Patterns ◽  
Negative Regulator ◽  
Female Rats ◽  
Delayed Puberty ◽  
Genome Wide Association Studies ◽  
Postnatal Maturation ◽  
Rat Hypothalamus

Lin28 and Lin28b are related RNA-binding proteins that inhibit the maturation of miRNAs of the let-7 family and participate in the control of cellular stemness and early embryonic development. Considerable interest has arisen recently concerning other physiological roles of the Lin28/let-7 axis, including its potential involvement in the control of puberty, as suggested by genome-wide association studies and functional genomics. We report herein the expression profiles of Lin28 and let-7 members in the rat hypothalamus during postnatal maturation and in selected models of altered puberty. The expression patterns of c-Myc (upstream positive regulator of Lin28), mir-145 (negative regulator of c-Myc), and mir-132 and mir-9 (putative miRNA repressors of Lin28, predicted by bioinformatic algorithms) were also explored. In male and female rats, Lin28, Lin28b, and c-Myc mRNAs displayed very high hypothalamic expression during the neonatal period, markedly decreased during the infantile-to-juvenile transition and reached minimal levels before/around puberty. A similar puberty-related decline was observed for Lin28b in monkey hypothalamus but not in the rat cortex, suggesting species conservation and tissue specificity. Conversely, let-7a, let-7b, mir-132, and mir-145, but not mir-9, showed opposite expression profiles. Perturbation of brain sex differentiation and puberty, by neonatal treatment with estrogen or androgen, altered the expression ratios of Lin28/let-7 at the time of puberty. Changes in the c-Myc/Lin28b/let-7 pathway were also detected in models of delayed puberty linked to early photoperiod manipulation and, to a lesser extent, postnatal underfeeding or chronic subnutrition. Altogether, our data are the first to document dramatic changes in the expression of the Lin28/let-7 axis in the rat hypothalamus during the postnatal maturation and after different manipulations that disturb puberty, thus suggesting the potential involvement of developmental changes in hypothalamic Lin28/let-7 expression in the mechanisms permitting/leading to puberty onset.

Comparison of the expression patterns of five neural RNA binding proteins in theXenopus retina

2004 ◽  
Vol 481 (4) ◽  
pp. 331-339 ◽  
Author(s):  
Marcos A. Amato ◽  
S�bastien Boy ◽  
Emilie Arnault ◽  
Manon Girard ◽  
Alice Della Puppa ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns

scholarly journals Bovine oocytes and early embryos express Staufen and ELAVL RNA-binding proteins

Zygote ◽  
2008 ◽  
Vol 16 (2) ◽  
pp. 161-168 ◽  
Author(s):  
M.D. Calder ◽  
P. Madan ◽  
A.J. Watson
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Germinal Vesicle ◽  
Blastocyst Stage ◽  
Developmental Competence ◽  
Protein Distribution ◽  
Morula Stage ◽  
The Stability

SummaryRNA-binding proteins (RBP) influence RNA editing, localization, stability and translation and may contribute to oocyte developmental competence by regulating the stability and turnover of oogenetic mRNAs. The expression of Staufen 1 and 2 and ELAVL1, ELAVL2 RNA-binding proteins during cow early development was characterized. Cumulus–oocyte complexes were collected from slaughterhouse ovaries, matured, inseminated and subjected to embryo culture in vitro. Oocyte or preimplantation embryo pools were processed for RT-PCR and whole-mount immunofluorescence analysis of mRNA expression and protein distribution. STAU1 and STAU2 and ELAVL1 mRNAs and proteins were detected throughout cow preimplantation development from the germinal vesicle (GV) oocyte to the blastocyst stage. ELAVL2 mRNAs were detectable from the GV to the morula stage, whereas ELAVL2 protein was in all stages examined and localized to both cytoplasm and nuclei. The findings provide a foundation for investigating the role of RBPs during mammalian oocyte maturation and early embryogenesis.

Distinct expression patterns of insulin-like growth factor binding proteins 2 and 5 during fetal and postnatal development.

Endocrinology ◽  
1994 ◽  
Vol 134 (2) ◽  
pp. 954-962 ◽  
Author(s):  
B N Green ◽  
S B Jones ◽  
R D Streck ◽  
T L Wood ◽  
P Rotwein ◽  
...  
Keyword(s):  
Growth Factor ◽  
Postnatal Development ◽  
Binding Proteins ◽  
Expression Patterns ◽  
Insulin Like Growth Factor ◽  
Factor Binding

scholarly journals The ALBA RNA-binding proteins function redundantly to promote growth and flowering in Arabidopsis

2019 ◽  
Author(s):  
Naiqi Wang ◽  
Meachery Jalajakumari ◽  
Thomas Miller ◽  
Mohsen Asadi ◽  
Anthony A Millar
Keyword(s):  
Gene Expression ◽  
Protein Function ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Short Form ◽  
Expression Patterns ◽  
Wild Type ◽  
Long Form ◽  
Mrna Binding

AbstractRNA-binding proteins (RBPs) are critical regulators of gene expression, but have been poorly studied relative to other classes of gene regulators. Recently, mRNA-interactome capture identified many Arabidopsis RBPs of unknown function, including a family of ALBA domain containing proteins. Arabidopsis has three short-form ALBA homologues (ALBA1-3) and three long-form ALBA homologues (ALBA4-6), both of which are conserved throughout the plant kingdom. Despite this ancient origin, ALBA-GUS translational fusions of ALBA1, ALBA2, ALBA4, and ALBA5 had indistinguishable expression patterns, all being preferentially expressed in young, rapidly dividing tissues. Likewise, all four ALBA proteins had indistinguishable ALBA-GFP subcellular localizations in roots, all being preferentially located to the cytoplasm, consistent with being mRNA-binding. Genetic analysis demonstrated redundancy within the long-form ALBA family members; in contrast to single alba mutants that all appeared wild-type, a triple alba456 mutant had slower rosette growth and a strong delay in flowering-time. RNA-sequencing found most differentially expressed genes in alba456 were related to metabolism, not development. Additionally, changes to the alba456 transcriptome were subtle, suggesting ALBA4-6 participates in a process that does not strongly affect transcriptome composition. Together, our findings demonstrate that ALBA protein function is highly redundant, and is essential for proper growth and flowering in Arabidopsis.HighlightThe RNA-binding ALBA proteins have indistinguishable expression patterns and subcellular localizations in Arabidopsis, acting redundantly to promote growth and flowering via a mechanism that does not strongly affect transcriptome composition.

Biology of the fragile X mental retardation protein, an RNA-binding protein

1999 ◽  
Vol 77 (4) ◽  
pp. 331-342 ◽  
Author(s):  
Edouard W Khandjian
Keyword(s):  
Mental Retardation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Trinucleotide Repeat ◽  
Rna Binding Proteins ◽  
Cpg Island ◽  
Fragile X ◽  
Expression Patterns ◽  
Fmr1 Gene ◽  
Nucleocytoplasmic Trafficking

The fragile X syndrome, an X-linked disease, is the most frequent cause of inherited mental retardation. The syndrome results from the absence of expression of the FMR1 gene (fragile mental retardation 1) owing to the expansion of a CGG trinucleotide repeat located in the 5prime untranslated region of the gene and the subsequent methylation of its CpG island. The FMR1 gene product (FMRP) is a cytoplasmic protein that contains two KH domains and one RGG box, characteristics of RNA-binding proteins. FMRP is associated with mRNP complexes containing poly(A)+mRNA within actively translating polyribosomes and contains nuclear localization and export signals making it a putative transporter (chaperone) of mRNA from the nucleus to the cytoplasm. FMRP is the archetype of a novel family of cytoplasmic RNA-binding proteins that includes FXR1P and FXR2P. Both of these proteins are very similar in overall structure to FMRP and are also associated with cytoplasmic mRNPs. Members of the FMR family are widely expressed in mouse and human tissues, albeit at various levels, and seem to play a subtle choreography of expression. FMRP is most abundant in neurons and is absent in muscle. FXR1P is strongly expressed in muscle and low levels are detected in neurons. The complex expression patterns of the FMR1 gene family in different cells and tissues suggest that independent, however similar, functions for each of the three FMR-related proteins might be expected in the selection and metabolism of tissue-specific classes of mRNA. The molecular mechanisms altered in cells lacking FMRP still remain to be elucidated as well as the putative role(s) of FXR1P and FXR2P as compensatory molecules.Key words: RNA-binding proteins, polyribosomes, messenger ribonucleoprotein, messenger ribonucleoparticles, nucleocytoplasmic trafficking, mental retardation.

scholarly journals Stress-Specific Spatiotemporal Responses of RNA-Binding Proteins in Human Stem Cell-Derived Motor Neurons

2020 ◽  
Vol 21 (21) ◽  
pp. 8346
Author(s):  
Jasmine Harley ◽  
Rickie Patani
Keyword(s):  
Stem Cell ◽  
Motor Neurons ◽  
Neurodegenerative Disorders ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Dependent Manner ◽  
Protein Distribution ◽  
Human Motor ◽  
Stress Dependent

RNA-binding proteins (RBPs) have been shown to play a key role in the pathogenesis of a variety of neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is an exemplar neurodegenerative disease characterised by rapid progression and relatively selective motor neuron loss. Nuclear-to-cytoplasmic mislocalisation and accumulation of RBPs have been identified as a pathological hallmark of the disease, yet the spatiotemporal responses of RBPs to different extrinsic stressors in human neurons remain incompletely understood. Here, we used healthy induced pluripotent stem cell (iPSC)-derived motor neurons to model how different types of cellular stress affect the nucleocytoplasmic localisation of key ALS-linked RBPs. We found that osmotic stress robustly induced nuclear loss of TDP-43, SPFQ, FUS, hnRNPA1 and hnRNPK, with characteristic changes in nucleocytoplasmic localisation in an RBP-dependent manner. Interestingly, we found that RBPs displayed stress-dependent characteristics, with unique responses to both heat and oxidative stress. Alongside nucleocytoplasmic protein distribution changes, we identified the formation of stress- and RBP-specific nuclear and cytoplasmic foci. Furthermore, the kinetics of nuclear relocalisation upon recovery from extrinsic stressors was also found to be both stress- and RBP-specific. Importantly, these experiments specifically highlight TDP-43 and FUS, two of the most recognised RBPs in ALS pathogenesis, as exhibiting delayed nuclear relocalisation following stress in healthy human motor neurons as compared to SFPQ, hnRNPA1 and hnRNPK. Notably, ALS-causing valosin containing protein (VCP) mutations did not disrupt the relocalisation dynamics of TDP-43 or FUS in human motor neurons following stress. An increased duration of TDP-43 and FUS within the cytoplasm after stress may render the environment more aggregation-prone, which may be poorly tolerated in the context of ALS and related neurodegenerative disorders. In summary, our study addresses stress-specific spatiotemporal responses of neurodegeneration-related RBPs in human motor neurons. The insights into the nucleocytoplasmic dynamics of RBPs provided here may be informative for future studies examining both disease mechanisms and therapeutic strategy.

scholarly journals Poly(A)-binding proteins and mRNA localization: who rules the roost?

2015 ◽  
Vol 43 (6) ◽  
pp. 1277-1284 ◽  
Author(s):  
Nicola K. Gray ◽  
Lenka Hrabálková ◽  
Jessica P. Scanlon ◽  
Richard W.P. Smith
Keyword(s):  
Steady State ◽  
Viral Infection ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cellular Stress ◽  
Mrna Translation ◽  
Mrna Localization ◽  
Cellular Distribution ◽  
Protein Partners

RNA-binding proteins are often multifunctional, interact with a variety of protein partners and display complex localizations within cells. Mammalian cytoplasmic poly(A)-binding proteins (PABPs) are multifunctional RNA-binding proteins that regulate multiple aspects of mRNA translation and stability. Although predominantly diffusely cytoplasmic at steady state, they shuttle through the nucleus and can be localized to a variety of cytoplasmic foci, including those associated with mRNA storage and localized translation. Intriguingly, PABP sub-cellular distribution can alter dramatically in response to cellular stress or viral infection, becoming predominantly nuclear and/or being enriched in induced cytoplasmic foci. However, relatively little is known about the mechanisms that govern this distribution/relocalization and in many cases PABP functions within specific sites remain unclear. Here we discuss the emerging evidence with respect to these questions in mammals.

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