scholarly journals Before It Gets Started: Regulating Translation at the 5′ UTR

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Patricia R. Araujo ◽  
Kihoon Yoon ◽  
Daijin Ko ◽  
Andrew D. Smith ◽  
Mei Qiao ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Elements ◽  
Open Reading Frame ◽  
Upstream Open Reading Frame ◽  
Translation Regulation ◽  
Binding Motifs ◽  
Reading Frame ◽  
Physiological Conditions ◽  
The Impact

Translation regulation plays important roles in both normal physiological conditions and diseases states. This regulation requires cis-regulatory elements located mostly in 5′ and 3′ UTRs and trans-regulatory factors (e.g., RNA binding proteins (RBPs)) which recognize specific RNA features and interact with the translation machinery to modulate its activity. In this paper, we discuss important aspects of 5′ UTR-mediated regulation by providing an overview of the characteristics and the function of the main elements present in this region, like uORF (upstream open reading frame), secondary structures, and RBPs binding motifs and different mechanisms of translation regulation and the impact they have on gene expression and human health when deregulated.

The Drosophila suppressor of sable gene encodes a polypeptide with regions similar to those of RNA-binding proteins

1991 ◽  
Vol 11 (2) ◽  
pp. 894-905
Author(s):  
R A Voelker ◽  
W Gibson ◽  
J P Graves ◽  
J F Sterling ◽  
M T Eisenberg
Keyword(s):  
Rna Processing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Open Reading Frame ◽  
In Vitro Translation ◽  
Rna Recognition Motif ◽  
Reading Frame ◽  
Cdna Sequences ◽  
Suppressor Of Sable

The nucleotide sequence of the Drosophila melanogaster suppressor of sable [su(s)] gene has been determined. Comparison of genomic and cDNA sequences indicates that an approximately 7,860-nucleotide primary transcript is processed into an approximately 5-kb message, expressed during all stages of the life cycle, that contains an open reading frame capable of encoding a 1,322-amino-acid protein of approximately 150 kDa. The putative protein contains an RNA recognition motif-like region and a highly charged arginine-, lysine-, serine-, aspartic or glutamic acid-rich region that is similar to a region contained in several RNA-processing proteins. In vitro translation of in vitro-transcribed RNA from a complete cDNA yields a product whose size agrees with the size predicted by the open reading frame. Antisera against su(s) fusion proteins recognize the in vitro-translated protein and detect a protein of identical size in the nuclear fractions from tissue culture cells and embryos. The protein is also present in smaller amounts in cytoplasmic fractions of embryos. That the su(s) protein has regions similar in structure to RNA-processing protein is consistent with its known role in affecting the transcript levels of those alleles that it suppresses.

scholarly journals The Drosophila suppressor of sable gene encodes a polypeptide with regions similar to those of RNA-binding proteins.

1991 ◽  
Vol 11 (2) ◽  
pp. 894-905 ◽  
Author(s):  
R A Voelker ◽  
W Gibson ◽  
J P Graves ◽  
J F Sterling ◽  
M T Eisenberg
Keyword(s):  
Rna Processing ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Open Reading Frame ◽  
In Vitro Translation ◽  
Rna Recognition Motif ◽  
Reading Frame ◽  
Cdna Sequences ◽  
Suppressor Of Sable

The nucleotide sequence of the Drosophila melanogaster suppressor of sable [su(s)] gene has been determined. Comparison of genomic and cDNA sequences indicates that an approximately 7,860-nucleotide primary transcript is processed into an approximately 5-kb message, expressed during all stages of the life cycle, that contains an open reading frame capable of encoding a 1,322-amino-acid protein of approximately 150 kDa. The putative protein contains an RNA recognition motif-like region and a highly charged arginine-, lysine-, serine-, aspartic or glutamic acid-rich region that is similar to a region contained in several RNA-processing proteins. In vitro translation of in vitro-transcribed RNA from a complete cDNA yields a product whose size agrees with the size predicted by the open reading frame. Antisera against su(s) fusion proteins recognize the in vitro-translated protein and detect a protein of identical size in the nuclear fractions from tissue culture cells and embryos. The protein is also present in smaller amounts in cytoplasmic fractions of embryos. That the su(s) protein has regions similar in structure to RNA-processing protein is consistent with its known role in affecting the transcript levels of those alleles that it suppresses.

scholarly journals SMDB: pivotal somatic sequence alterations reprogramming regulatory cascades

NAR Cancer ◽  
2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Limin Jiang ◽  
Mingrui Duan ◽  
Fei Guo ◽  
Jijun Tang ◽  
Olufunmilola Oybamiji ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Translation Regulation ◽  
Single Nucleotide ◽  
Binding Motifs ◽  
Sequence Alteration ◽  
Regulatory Cascades ◽  
Gains And Losses

Abstract Binding motifs for transcription factors, RNA-binding proteins, microRNAs (miRNAs), etc. are vital for proper gene transcription and translation regulation. Sequence alteration mechanisms including single nucleotide mutations, insertion, deletion, RNA editing and single nucleotide polymorphism can lead to gains and losses of binding motifs; such consequentially emerged or vanished binding motifs are termed ‘somatic motifs’ by us. Somatic motifs have been studied sporadically but have never been curated into a comprehensive resource. By analyzing various types of sequence altering data from large consortiums, we successfully identified millions of somatic motifs, including those for important transcription factors, RNA-binding proteins, miRNA seeds and miRNA–mRNA 3′-UTR target motifs. While a few of these somatic motifs have been well studied, our results contain many novel somatic motifs that occur at high frequency and are thus likely to cause important biological repercussions. Genes targeted by these altered motifs are excellent candidates for further mechanism studies. Here, we present the first database that hosts millions of somatic motifs ascribed to a variety of sequence alteration mechanisms.

scholarly journals The 3′-untranslated region of the Ste20-like kinase SLK regulates SLK expression

2007 ◽  
Vol 292 (2) ◽  
pp. F845-F852 ◽  
Author(s):  
Andrey V. Cybulsky ◽  
Tomoko Takano ◽  
Joan Papillon ◽  
Wen Hao ◽  
Arturo Mancini ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mrna Stability ◽  
Untranslated Region ◽  
Kidney Development ◽  
Rna Binding ◽  
Fluorescent Protein ◽  
Rna Binding Proteins ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Glomerular Epithelial Cells

Ste20-like kinase, SLK, a germinal center kinase found in kidney epithelial cells, signals to promote apoptosis. Expression of SLK mRNA and protein and kinase activity are increased during kidney development and recovery from ischemic acute renal failure. The 3′-untranslated region (3′-UTR) of SLK mRNA contains multiple adenine and uridine-rich elements, suggesting that 3′-UTR may regulate mRNA stability. This was confirmed in COS cell transient transfection studies, which showed that expression of the SLK open-reading frame plus 3′-UTR mRNA was reduced by 35% relative to the open-reading frame alone. To further characterize the SLK-3′-UTR, this nucleotide sequence was subcloned downstream of enhanced green fluorescent protein (EGFP) cDNA. In COS, 293T, and glomerular epithelial cells, expression of EGFP mRNA and protein was markedly reduced in the presence of the SLK-3′-UTR. After transfection and subsequent addition of actinomycin D, EGFP mRNA remained stable in cells for at least 6 h, whereas EGFP-SLK-3′-UTR mRNA decayed with a half-life of ∼4 h. A region containing five AUUUA motifs within the SLK-3′-UTR destabilized EGFP mRNA. Deletion of this region from the SLK-3′-UTR, in part, restored mRNA stability. By UV cross-linking and SDS-PAGE, the SLK-3′-UTR bound to protein(s) of ∼30 kDa in extracts of COS cells, glomerular epithelial cells, and kidney. Cotransfection of HuR (a RNA binding protein of ∼30 kDa) increased the steady-state mRNA level of EGFP-SLK-3′-UTR but not EGFP. Thus the SLK-3′-UTR may interact with kidney RNA-binding proteins to regulate expression of SLK mRNA during kidney development and after ischemic injury.

scholarly journals RNA m6A modification orchestrates a LINE-1–host interaction that facilitates retrotransposition and contributes to long gene vulnerability

Cell Research ◽  
2021 ◽  
Author(s):  
Feng Xiong ◽  
Ruoyu Wang ◽  
Joo-Hyung Lee ◽  
Shenglan Li ◽  
Shin-Fu Chen ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulatory Elements ◽  
Host Interaction ◽  
Damage Repair ◽  
Novel Host ◽  
Cell Type Specific ◽  
Human Fetal Tissues ◽  
Long Genes

AbstractThe molecular basis underlying the interaction between retrotransposable elements (RTEs) and the human genome remains poorly understood. Here, we profiled N6-methyladenosine (m6A) deposition on nascent RNAs in human cells by developing a new method MINT-Seq, which revealed that many classes of RTE RNAs, particularly intronic LINE-1s (L1s), are strongly methylated. These m6A-marked intronic L1s (MILs) are evolutionarily young, sense-oriented to hosting genes, and are bound by a dozen RNA binding proteins (RBPs) that are putative novel readers of m6A-modified RNAs, including a nuclear matrix protein SAFB. Notably, m6A positively controls the expression of both autonomous L1s and co-transcribed L1 relics, promoting L1 retrotransposition. We showed that MILs preferentially reside in long genes with critical roles in DNA damage repair and sometimes in L1 suppression per se, where they act as transcriptional “roadblocks” to impede the hosting gene expression, revealing a novel host-weakening strategy by the L1s. In counteraction, the host uses the SAFB reader complex to bind m6A-L1s to reduce their levels, and to safeguard hosting gene transcription. Remarkably, our analysis identified thousands of MILs in multiple human fetal tissues, enlisting them as a novel category of cell-type-specific regulatory elements that often compromise transcription of long genes and confer their vulnerability in neurodevelopmental disorders. We propose that this m6A-orchestrated L1–host interaction plays widespread roles in gene regulation, genome integrity, human development and diseases.

scholarly journals Current insights into the implications of m6A RNA methylation and autophagy interaction in human diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuechai Chen ◽  
Jianan Wang ◽  
Muhammad Tahir ◽  
Fangfang Zhang ◽  
Yuanyuan Ran ◽  
...  
Keyword(s):  
Intervertebral Disc Degeneration ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Degradation Process ◽  
Human Diseases ◽  
Rna Modification ◽  
Rna Methylation ◽  
M6a Rna Methylation ◽  
The Impact

AbstractAutophagy is a conserved degradation process crucial to maintaining the primary function of cellular and organismal metabolism. Impaired autophagy could develop numerous diseases, including cancer, cardiomyopathy, neurodegenerative disorders, and aging. N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells, and the fate of m6A modified transcripts is controlled by m6A RNA binding proteins. m6A modification influences mRNA alternative splicing, stability, translation, and subcellular localization. Intriguingly, recent studies show that m6A RNA methylation could alter the expression of essential autophagy-related (ATG) genes and influence the autophagy function. Thus, both m6A modification and autophagy could play a crucial role in the onset and progression of various human diseases. In this review, we summarize the latest studies describing the impact of m6A modification in autophagy regulation and discuss the role of m6A modification-autophagy axis in different human diseases, including obesity, heart disease, azoospermatism or oligospermatism, intervertebral disc degeneration, and cancer. The comprehensive understanding of the m6A modification and autophagy interplay may help in interpreting their impact on human diseases and may aid in devising future therapeutic strategies.

scholarly journals Sequence and structure of mtr, an amino acid transport gene of Neurospora crassa

Genome ◽  
1991 ◽  
Vol 34 (4) ◽  
pp. 644-651 ◽  
Author(s):  
Kenneth Koo ◽  
W. Dorsey Stuart
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Neurospora Crassa ◽  
Rna Binding ◽  
Signal Sequence ◽  
Average Length ◽  
Open Reading Frame ◽  
Mrna Transcript ◽  
S1 Nuclease ◽  
Reading Frame

The gene product of the mtr locus of Neurospora crassa is required for the transport of neutral aliphatic and aromatic amino acids via the N system. We have previously cloned three cosmids containing Neurospora DNA that complement the mtr-6(r) mutant allele. The cloned DNAs were tightly linked to restriction fragment length polymorphisms that flank the mtr locus. A 2.9-kbp fragment from one cosmid was subcloned and found to complement the mtr-6(r) allele. Here we report the sequence of the fragment that hybridized to a poly(A)+ mRNA transcript of about 2300 nucleotides. We have identified an 845-bp open reading frame (ORF) having a 59-bp intron as the potential mtr ORF. S1 nuclease analysis of the transcript confirmed the transcript size and the presence of the intron. A second open reading frame was found upstream in the same reading frame as the mtr ORF and appears to be present in the mRNA transcript. The mtr ORF is predicted to encode a 261 amino acid polypeptide with a molecular mass of 28 613 Da. The proposed polypeptide exhibits six potential α-helical transmembrane domains with an average length of 23 amino acids, does not have a signal sequence, and contains amino acid sequence homologous to an RNA binding motif.Key words: sequence, membranes, ribonucleoprotein.

scholarly journals Sucrose Control of Translation Mediated by an Upstream Open Reading Frame-Encoded Peptide

2009 ◽  
Vol 150 (3) ◽  
pp. 1356-1367 ◽  
Author(s):  
Fatemeh Rahmani ◽  
Maureen Hummel ◽  
Jolanda Schuurmans ◽  
Anika Wiese-Klinkenberg ◽  
Sjef Smeekens ◽  
...  
Keyword(s):  
Open Reading Frame ◽  
Upstream Open Reading Frame ◽  
Reading Frame

scholarly journals Translational regulation of Arabidopsis XIPOTL1 is modulated by phosphocholine levels via the phylogenetically conserved upstream open reading frame 30

2012 ◽  
Vol 63 (14) ◽  
pp. 5203-5221 ◽  
Author(s):  
Fulgencio Alatorre-Cobos ◽  
Alfredo Cruz-Ramírez ◽  
Celine A. Hayden ◽  
Claudia-Anahí Pérez-Torres ◽  
Anne-Laure Chauvin ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Open Reading Frame ◽  
Upstream Open Reading Frame ◽  
Reading Frame
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