scholarly journals Translation efficiency of zein mRNA is reduced by hybrid formation between the 5′- and 3′-untranslated region

1985 ◽  
Vol 4 (9) ◽  
pp. 2153-2158 ◽  
Author(s):  
A. Spena ◽  
E. Krause ◽  
B. Dobberstein
Keyword(s):  
Untranslated Region ◽  
Translation Efficiency ◽  
Hybrid Formation ◽  
Zein Mrna

scholarly journals Functional interplay between DEAD-box RNA helicases Ded1 and Dbp1 in preinitiation complex attachment and scanning on structured mRNAs in vivo

2019 ◽  
Author(s):  
Neelam Dabas Sen ◽  
Neha Gupta ◽  
Stuart K. Archer ◽  
Thomas Preiss ◽  
Jon R Lorsch ◽  
...  
Keyword(s):  
Untranslated Region ◽  
Double Mutant ◽  
Direct Evidence ◽  
Translation Efficiency ◽  
Rna Structures ◽  
Preinitiation Complex ◽  
Rna Helicases ◽  
Ribosome Binding ◽  
Dead Box

Abstract RNA structures that impede ribosome binding or subsequent scanning of the 5′-untranslated region (5′-UTR) for the AUG initiation codon reduce translation efficiency. Yeast DEAD-box RNA helicase Ded1 appears to promote translation by resolving 5′-UTR structures, but whether its paralog, Dbp1, performs similar functions is unknown. Furthermore, direct in vivo evidence was lacking that Ded1 or Dbp1 resolves 5′-UTR structures that impede attachment of the 43S preinitiation complex (PIC) or scanning. Here, profiling of translating 80S ribosomes reveals that the translational efficiencies of many more mRNAs are reduced in a ded1-ts dbp1Δ double mutant versus either single mutant, becoming highly dependent on Dbp1 or Ded1 only when the other helicase is impaired. Such ‘conditionally hyperdependent’ mRNAs contain unusually long 5′-UTRs with heightened propensity for secondary structure and longer transcript lengths. Consistently, overexpressing Dbp1 in ded1 cells improves the translation of many such Ded1-hyperdependent mRNAs. Importantly, Dbp1 mimics Ded1 in conferring greater acceleration of 48S PIC assembly in a purified system on mRNAs harboring structured 5′-UTRs. Profiling 40S initiation complexes in ded1 and dbp1 mutants provides direct evidence that Ded1 and Dbp1 cooperate to stimulate both PIC attachment and scanning on many Ded1/Dbp1-hyperdependent mRNAs in vivo.

scholarly journals Reduced translation efficiency due to novel splicing variants in 5′ untranslated region and identification of novel cis-regulatory elements in canine and human BRCA2

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yasunaga Yoshikawa ◽  
Hajime Kozuma ◽  
Masami Morimatsu ◽  
Kaori Sugawara ◽  
Koichi Orino
Keyword(s):  
Homologous Recombination ◽  
Untranslated Region ◽  
Cultured Cells ◽  
Regulatory Elements ◽  
Expression Level ◽  
Serum Starvation ◽  
Translational Efficiency ◽  
Translation Efficiency ◽  
Intron 1 ◽  
Splicing Variants

Abstract Background Breast cancer 2, early onset (BRCA2) is a tumor suppressor gene. The protein encoded by this gene plays an important role in homologous recombination (HR)-mediated DNA repair. Deleterious mutations in BRCA2 and downregulation of its expression have been associated with tumorigenesis in dogs and humans. Thus, regulation of BRCA2 expression level is important for maintaining homeostasis in homologous recombination. Results In this study, the mechanisms that regulate the expression of BRCA2 were proposed. Novel splicing variants were identified in the 5′ untranslated region (UTR) of canine and human BRCA2 in canine testis, canine ovary, and canine and human cultured cell lines. In cultured cells, the ratio of BRCA2 splicing variants at the 5′ UTR was altered by serum starvation. These novel splicing variants, excluding one of the canine splicing variants, were found to reduce the translational efficiency. Additionally, the DNA sequence in human BRCA2 intron 1 harbored novel cis-regulatory elements. Three silencer and two enhancer cis-regulatory elements were identified in human BRCA2 intron 1. Conclusions This study demonstrates that BRCA2 expression level is regulated via 5′ UTR splicing variants and that the BRCA2 intron 1 region harbors cis-regulatory elements.

3' Untranslated Region (UTR) Alterations Are Frequently Targeted By MM-Related Mirnas and Affects the Clinical Outcome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4447-4447
Author(s):  
Mehmet K. Samur ◽  
Irtisha Singh ◽  
Lee Shih-Han ◽  
Adam Samuel Sperling ◽  
Mariateresa Fulciniti ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Clinical Outcome ◽  
Untranslated Region ◽  
High Throughput Sequencing ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Protein Localization ◽  
Median Frequency ◽  
Translation Efficiency ◽  
Normal Plasma

Abstract More than half of human genes use alternative cleavage and polyadenylation to generate alternative 3' untranslated region (3'UTR) isoforms that play a role in gene expression regulation. The 3' untranslated region (3'UTR) of mRNA contains elements that play regulatory roles in polyadenylation, localization, translation efficiency, and mRNA stability. Although relative contributions of different regulatory mechanisms remain poorly understood, several recent studies showed that alterations in 3'UTRs might affect protein localization as well as their interactions with other proteins. Here, we obtained global measurements of 3' UTR sequencing and RNA-seq in MM and normal plasma cells to study the effects of 3'UTR alterations in MM. Whole transcriptome sequencing (RNAseq) data from 420 uniformly treated newly diagnosed MM samples were compared with 18 normal plasma cell by using dynamic analyses of alternative PolyAdenylation and results were compared with alternative 3'UTR isoforms measured using 3'-seq, an established quantitative 3' end sequencing method from 15 samples pilot study. We observed ~10000 different isoforms with a median frequency of 297 (range 1-2495) altered 3'UTRs per sample. We observed 563 isoforms that have distal alternative poly A (APA) site and 449 isoforms that have proximal APA site compared to normal plasma cells in at least 10% of our patients. Enrichment analysis showed that short UTR genes are significantly targeted by miR-506, miR-133, miR-130, miR-27, miR-181 and miR-200 (FDR q-value < 0.05). We also observed that expression of 90 genes significantly increased between those samples with shorter UTR vs. regular UTR. Longer UTR genes are enriched in mir-124, mir-186, mir-200, mir-302, mir-495 and expression of 123 genes were significantly downregulated between long UTR and others. There were no tumor suppressor genes and 8 oncogenes in short UTR genes and 4 tumor suppressor and 14 oncogenes in longer UTR genes. Our results were confirmed using the 3'seq study which showed that 170 genes have longer UTR in MM compared to normal plasma cells and 187 genes have shorter UTR. ~60% of longer and ~65% of shorter UTR genes reported by 3'seq were also observed with RNAseq. Furthermore, we focused on common genes reported by both high-throughput sequencing methods and analyzed any connection between outcome and UTR shortening or lengthening. We observed 26 genes with altered UTR regions have impact on PFS or OS. In conclusion, we report significant alternate UTR usage, including intronic UTRs in MM affecting the disease biology and clinical outcome. Our data suggests the need to further investigate the molecular impact of alternate UTR usage and its relationship with miR in myeloma. Disclosures No relevant conflicts of interest to declare.

scholarly journals IGF-I 3′ Untranslated Region: Strain-Specific Polymorphisms and Motifs Regulating IGF-I in Osteoblasts

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 253-262 ◽  
Author(s):  
Spenser S. Smith ◽  
Catherine B. Kessler ◽  
Vikram Shenoy ◽  
Clifford J. Rosen ◽  
Anne M. Delany
Keyword(s):  
Bone Mass ◽  
Untranslated Region ◽  
Osteoblastic Differentiation ◽  
Genotypic Differences ◽  
Translation Efficiency ◽  
Mrna Levels ◽  
Proximal Site ◽  
Igf I ◽  
C3h Mice ◽  
Exon 4

Reduced IGF-I is associated with low bone mass in humans and mice. C3H/He/J (C3H) mice have higher skeletal IGF-I and greater bone mass than C57BL/6J (B6). We hypothesized that strain-related genotypic differences in Igf1 affected skeletal function. The Igf1 coding region is nonpolymorphic, but its 3′ untranslated region (UTR) is polymorphic between C3H and B6. Luciferase-Igf1 3′ UTR reporter constructs showed that these polymorphic regions did not affect UTR function. IGF-I splice variants give rise to a common mature IGF-I peptide, but different E peptides. We identified two splice products, exon 4+6 (Ea) and exon 4+5+6 (Eb, mechano-growth factor) and found that their abundance was unchanged during osteoblastic differentiation. The Igf1 3′ UTR encoded by exon 6 contains alternative polyadenylation sites. Proximal site use produces a short 3′ UTR of approximately 195 bases, whereas distal site usage results in an approximately 6300-base UTR. Although Igf1 mRNA levels did not change during osteoblastic differentiation, distal polyadenylation site usage was increased in B6 cells but not in C3H. The resulting long Igf1 RNA isoform is less stable and has decreased translation efficiency, which may be one mechanism contributing to decreased IGF-I in B6 vs. C3H mice. Although the long UTR contains a conserved [GU]18 repeat, which is a positive regulator of UTR activity, it is also targeted by negative regulators, miR-29 and miR-365. These microRNAs are increased in B6 and C3H cells during osteoblastic differentiation. Differential expression of the long Igf1 3′ UTR isoform may be a possible mechanism for enhanced IGF-I regulation in B6 vs. C3H mice.

scholarly journals Mutation Analysis of the 5′ Untranslated Region of the Cold Shock cspA mRNA of Escherichia coli

1999 ◽  
Vol 181 (20) ◽  
pp. 6284-6291 ◽  
Author(s):  
Kunitoshi Yamanaka ◽  
Masanori Mitta ◽  
Masayori Inouye
Keyword(s):  
Escherichia Coli ◽  
Untranslated Region ◽  
Cold Shock ◽  
Cold Shock Protein ◽  
Translation Efficiency ◽  
Negative Effect ◽  
Downstream Box ◽  
The Stability ◽  
The Relationship ◽  
Positive Effect

ABSTRACT The mRNA for CspA, a major cold shock protein in Escherichia coli, contains an unusually long (159 bases) 5′ untranslated region (5′-UTR), and its stability has been shown to play a major role in cold shock induction of CspA. The 5′-UTR of the cspAmRNA has a negative effect on its expression at 37°C but has a positive effect upon cold shock. In this report, a series ofcspA-lacZ fusions having a 26- to 32-base deletion in the 5′-UTR were constructed to examine the roles of specific regions within the 5′-UTR in cspA expression. It was found that none of the deletion mutations had significant effects on the stability of mRNA at both 37 and 15°C. However, two mutations (Δ56-86 and Δ86-117) caused a substantial increase of β-galactosidase activity at 37°C, indicating that the deleted regions contain a negativecis element(s) for translation. A mutation (Δ2-27) deleting the highly conserved cold box sequence had little effect on cold shock induction of β-galactosidase. Interestingly, three mutations (Δ28-55, Δ86-117, and Δ118-143) caused poor cold shock induction of β-galactosidase. In particular, the Δ118-143 mutation reduced the translation efficiency of the cspA mRNA to less than 10% of that of the wild-type construct. The deleted region contains a 13-base sequence named upstream box (bases 123 to 135), which is highly conserved in cspA, cspB,cspG, and cspI, and is located 11 bases upstream of the Shine-Dalgarno (SD) sequence. The upstream box might be another cis element involved in translation efficiency of the cspA mRNA in addition to the SD sequence and the downstream box sequence. The relationship between the mRNA secondary structure and translation efficiency is discussed.

scholarly journals Reduced translation efficiency due to novel splicing variants in 5′ untranslated region and identification of novel cis-regulatory elements in canine and human BRCA2

2020 ◽  
Author(s):  
Yasunaga Yoshikawa ◽  
Hajime Kozuma ◽  
Masami Morimatsu ◽  
Kaori Sugawara ◽  
Koichi Orino
Keyword(s):  
Untranslated Region ◽  
Cultured Cells ◽  
Regulatory Elements ◽  
Suppressor Gene ◽  
Expression Level ◽  
Serum Starvation ◽  
Translational Efficiency ◽  
Translation Efficiency ◽  
Intron 1 ◽  
Splicing Variants

Abstract Background: Breast cancer 2, early onset (BRCA2) is a tumor suppressor gene. The protein encoded by this gene plays an important role in homologous recombination (HR)-mediated DNA repair. Deleterious mutations in BRCA2 and downregulation of its expression have been associated with tumorigenesis in dogs and humans. Thus, regulation of BRCA2 expression level is important for maintaining homeostasis in homologous recombination.Results: In this study, the mechanisms that regulate the expression of BRCA2 were proposed. Novel splicing variants were identified in the 5′ untranslated region (UTR) of canine and human BRCA2 in canine testis, canine ovary, and canine and human cultured cell lines. In cultured cells, the ratio of BRCA2 splicing variants at the 5′ UTR was altered by serum starvation. These novel splicing variants, excluding one of the canine splicing variants, were found to reduce the translational efficiency. Additionally, the DNA sequence in human BRCA2 intron 1 harbored novel cis-regulatory elements. Three silencer and two enhancer cis-regulatory elements were identified in human BRCA2 intron 1.Conclusions: This study demonstrates that BRCA2 expression level is regulated via 5′ UTR splicing variants and that the BRCA2 intron 1 region harbors cis-regulatory elements.

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