Deciphering the rules by which dynamics of mRNA secondary structure affect translation efficiency in Saccharomyces cerevisiae

Mao, Yuanhui; Liu, Huiling; Liu, Yanlin; Tao, Shiheng

doi:10.1093/nar/gku159

Cited by 82 publications

(110 citation statements)

References 58 publications

(67 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, translation elongation can be regulated by features contained within the ORF or nascent polypeptide (45,47,48). For example, codon usage (47), RNA structure (59,60), and certain nascent polypeptide sequences can alter the rate of ribosomal transit (45). It will be of interest to identify those features of flaviviral and cellular RNAs that confer a dependency on function of the ribosomal stalk proteins.…”

Section: Discussionmentioning

confidence: 99%

RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation

Campos

Wong

Xie

et al. 2017

J Virol

View full text Add to dashboard Cite

The Flavivirus genus contains several arthropod-borne viruses that pose global health threats, including dengue viruses (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). In order to understand how these viruses replicate in human cells, we previously conducted genome-scale RNA interference screens to identify candidate host factors. In these screens, we identified ribosomal proteins RPLP1 and RPLP2 (RPLP1/2) to be among the most crucial putative host factors required for DENV and YFV infection. RPLP1/2 are phosphoproteins that bind the ribosome through interaction with another ribosomal protein, RPLP0, to form a structure termed the ribosomal stalk. RPLP1/2 were validated as essential host factors for DENV, YFV, and ZIKV infection in two human cell lines: A549 lung adenocarcinoma and HuH-7 hepatoma cells, and for productive DENV infection of Aedes aegypti mosquitoes. Depletion of RPLP1/2 caused moderate cell-line-specific effects on global protein synthesis, as determined by metabolic labeling. In A549 cells, global translation was increased, while in HuH-7 cells it was reduced, albeit both of these effects were modest. In contrast, RPLP1/2 knockdown strongly reduced early DENV protein accumulation, suggesting a requirement for RPLP1/2 in viral translation. Furthermore, knockdown of RPLP1/2 reduced levels of DENV structural proteins expressed from an exogenous transgene. We postulate that these ribosomal proteins are required for efficient translation elongation through the viral open reading frame. In summary, this work identifies RPLP1/2 as critical flaviviral host factors required for translation.IMPORTANCE Flaviviruses cause important diseases in humans. Examples of mosquito-transmitted flaviviruses include dengue, yellow fever and Zika viruses. Viruses require a plethora of cellular factors to infect cells, and the ribosome plays an essential role in all viral infections. The ribosome is a complex macromolecular machine composed of RNA and proteins and it is responsible for protein synthesis. We identified two specific ribosomal proteins that are strictly required for flavivirus infection of human cells and mosquitoes: RPLP1 and RPLP2 (RPLP1/2). These proteins are part of a structure known as the ribosomal stalk and help orchestrate the elongation phase of translation. We show that flaviviruses are particularly dependent on the function of RPLP1/2. Our findings suggest that ribosome composition is an important factor for virus translation and may represent a regulatory layer for translation of specific cellular mRNAs. (1)(2)(3)(4). Dengue viruses (DENV-1 to -4), the most prevalent of all arthropod-borne viruses, infect approximately 390 million people per year (1); yellow fever virus (YFV), which causes life-threatening disease (5) has reemerged this year in Africa (6); Zika virus (ZIKV) is currently responsible for a pandemic in the Americas that has caused grave concern because of associations with birth defects and Guillain-Barré syndrome (3). KEYWORDS flavivirus, ribosomal proteins, tran...

show abstract

Section: Discussionmentioning

confidence: 99%

RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation

Campos

Wong

Xie

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…Studies on model oligonucleotides have shown that the presence of RNA secondary structure promotes ribosome pausing (126). However, in vivo, the situation is considerably more complicated, reflecting interplay between multiple parameters, including RNA structure, tRNA abundance, and codon choice (72). One study using in vitro structurome data from yeast (43) and in silicopredicted structures in E. coli proposed that rapid translation of codons associated with highly abundant tRNAs is offset by greater RNA structure associated with these codons, leading to a smoothing of translation rate (31).…”

Section: Stability and Degradationmentioning

confidence: 99%

Genome-Wide Analysis of RNA Secondary Structure

Bevilacqua¹,

Ritchey²,

et al. 2016

Annu. Rev. Genet.

204

157

View full text Add to dashboard Cite

Single-stranded RNA molecules fold into extraordinarily complicated secondary and tertiary structures as a result of intramolecular base pairing. In vivo, these RNA structures are not static. Instead, they are remodeled in response to changes in the prevailing physicochemical environment of the cell and as a result of intermolecular base pairing and interactions with RNAbinding proteins. Remarkable technical advances now allow us to probe RNA secondary structure at single-nucleotide resolution and genome-wide, both in vitro and in vivo. These data sets provide new glimpses into the RNA universe. Analyses of RNA structuromes in HIV, yeast, Arabidopsis, and mammalian cells and tissues have revealed regulatory effects of RNA structure on messenger RNA (mRNA) polyadenylation, splicing, translation, and turnover. Application of new methods for genome-wide identification of mRNA modifications, particularly methylation and pseudouridylation, has shown that the RNA "epitranscriptome" both influences and is influenced by RNA structure. In this review, we describe newly developed genome-wide RNA structure-probing methods and synthesize the information emerging from their application.

show abstract

“…This type of ribosome queuing has been much studied in theoretical approaches [78][79][80][81], and is a complex function of the distribution of codon speeds in different parts of an mRNA. While dense packing of ribosomes generally leads to slower ribosome movement because of collisions, it was also suggested that dense packing can negate the effect of secondary structures which cannot reform between ribosomes that follow each other closely [82].…”

Section: From Trna Selection To Ribosomal Speedmentioning

confidence: 99%

Synonymous codons, ribosome speed, and eukaryotic gene expression regulation

Tarrant

Haar

2014

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Quantitative control of gene expression occurs at multiple levels, including the level of translation. Within the overall process of translation, most identified regulatory processes impinge on the initiation phase. However, recent studies have revealed that the elongation phase can also regulate translation if elongation and initiation occur with specific, not mutually compatible rate parameters. Translation elongation then limits the overall amount of protein that can be made from an mRNA. Several recently discovered control mechanisms of biological pathways are based on such elongation control. Here, we review the molecular mechanisms that determine ribosome speed in eukaryotic organisms, and discuss under which conditions ribosome speed can become the controlling parameter of gene expression levels.

show abstract

Deciphering the rules by which dynamics of mRNA secondary structure affect translation efficiency in Saccharomyces cerevisiae

Cited by 82 publications

References 58 publications

RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation

RPLP1 and RPLP2 Are Essential Flavivirus Host Factors That Promote Early Viral Protein Accumulation

Genome-Wide Analysis of RNA Secondary Structure

Synonymous codons, ribosome speed, and eukaryotic gene expression regulation

Contact Info

Product

Resources

About