scholarly journals The Role of the 3′ Untranslated Region in mRNA Sorting to the Vicinity of Mitochondria Is Conserved from Yeast to Human Cells

2003 ◽  
Vol 14 (9) ◽  
pp. 3848-3856 ◽  
Author(s):  
J. Sylvestre ◽  
A. Margeot ◽  
C. Jacq ◽  
G. Dujardin ◽  
M. Corral-Debrinski

We recently demonstrated, using yeast DNA microarrays, that mRNAs of polysomes that coisolate with mitochondria code for a subset of mitochondrial proteins. The majority of these mRNAs encode proteins of prokaryotic origin. Herein, we show that a similar association occurs between polysomes and mitochondria in human cells. To determine whether mRNA transport machinery is conserved from yeast to human cells, we examined the subcellular localization of human OXA1 mRNA in yeast. Oxa1p is a key component in the biogenesis of mitochondrial inner membrane and is conserved from bacteria to eukaryotic organelles. The expression of human OXA1 cDNA partially restores the respiratory capacity of yeast oxa1– cells. In this study, we demonstrate that 1) OXA1 mRNAs are remarkably enriched in mitochondrion-bound polysomes purified from yeast and human cells; 2) the presence of the human OXA1 3′ untranslated region (UTR) is required for the function of the human Oxa1p inside yeast mitochondria; and 3) the accurate sorting of the human OXA1 mRNA to the vicinity of yeast mitochondria is due to the recognition by yeast proteins of the human 3′ UTR. Therefore, it seems that the recognition mechanism of OXA1 3′ UTR is conserved throughout evolution and is necessary for Oxa1p function.

2000 ◽  
Vol 20 (21) ◽  
pp. 7881-7892 ◽  
Author(s):  
M. Corral-Debrinski ◽  
C. Blugeon ◽  
C. Jacq

ABSTRACT We isolated mitochondria from Saccharomyces cerevisiaeto selectively study polysomes bound to the mitochondrial surface. The distribution of several mRNAs coding for mitochondrial proteins was examined in free and mitochondrion-bound polysomes. Some mRNAs exclusively localize to mitochondrion-bound polysomes, such as the ones coding for Atm1p, Cox10p, Tim44p, Atp2p, and Cot1p. In contrast, mRNAs encoding Cox6p, Cox5a, Aac1p, and Mir1p are found enriched in free cytoplasmic polysome fractions. Aac1p and Mir1p are transporters that lack cleavable presequences. Sequences required for mRNA asymmetric subcellular distribution were determined by analyzing the localization of reporter mRNAs containing the presequence coding region and/or the 3′-untranslated region (3′UTR) of ATM1, a gene encoding an ABC transporter of the mitochondrial inner membrane. Biochemical analyses of mitochondrion-bound polysomes and direct visualization of RNA localization in living yeast cells allowed us to demonstrate that either the presequence coding region or the 3′UTR ofATM1 is sufficient to allow the reporter mRNA to localize to the vicinity of the mitochondrion, independently of its translation. These data demonstrate that mRNA localization is one of the mechanisms used, in yeast, for segregating mitochondrial proteins.


2020 ◽  
Vol 34 (5) ◽  
pp. 6703-6717 ◽  
Author(s):  
Pieter A. Leermakers ◽  
Alexander H. V. Remels ◽  
Marijke I. Zonneveld ◽  
Kasper M. A. Rouschop ◽  
Annemie M. W. J. Schols ◽  
...  

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1026
Author(s):  
Elisa Chiodi ◽  
Allison M. Marn ◽  
Matthew T. Geib ◽  
M. Selim Ünlü

The importance of microarrays in diagnostics and medicine has drastically increased in the last few years. Nevertheless, the efficiency of a microarray-based assay intrinsically depends on the density and functionality of the biorecognition elements immobilized onto each sensor spot. Recently, researchers have put effort into developing new functionalization strategies and technologies which provide efficient immobilization and stability of any sort of molecule. Here, we present an overview of the most widely used methods of surface functionalization of microarray substrates, as well as the most recent advances in the field, and compare their performance in terms of optimal immobilization of the bioreceptor molecules. We focus on label-free microarrays and, in particular, we aim to describe the impact of surface chemistry on two types of microarray-based sensors: microarrays for single particle imaging and for label-free measurements of binding kinetics. Both protein and DNA microarrays are taken into consideration, and the effect of different polymeric coatings on the molecules’ functionalities is critically analyzed.


BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 390-393
Author(s):  
F.-Nora Vögtle

AbstractThe majority of mitochondrial proteins are encoded in the nuclear genome, so that the nearly entire proteome is assembled by post-translational preprotein import from the cytosol. Proteomic imbalances are sensed and induce cellular stress response pathways to restore proteostasis. Here, the mitochondrial presequence protease MPP serves as example to illustrate the critical role of mitochondrial protein biogenesis and proteostasis on cellular integrity.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao-Miao Zhao ◽  
Wei-Li Yang ◽  
Fang-Yuan Yang ◽  
Li Zhang ◽  
Wei-Jin Huang ◽  
...  

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.


2021 ◽  
pp. 104832
Author(s):  
Rafael Marchi ◽  
Bruna Sugita ◽  
Ariana Centa ◽  
Aline S. Fonseca ◽  
Stefanne Bortoletto ◽  
...  

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 486
Author(s):  
Sílvia C. Rodrigues ◽  
Renato M. S. Cardoso ◽  
Filipe V. Duarte

The most famous role of mitochondria is to generate ATP through oxidative phosphorylation, a metabolic pathway that involves a chain of four protein complexes (the electron transport chain, ETC) that generates a proton-motive force that in turn drives the ATP synthesis by the Complex V (ATP synthase). An impressive number of more than 1000 mitochondrial proteins have been discovered. Since mitochondrial proteins have a dual genetic origin, it is predicted that ~99% of these proteins are nuclear-encoded and are synthesized in the cytoplasmatic compartment, being further imported through mitochondrial membrane transporters. The lasting 1% of mitochondrial proteins are encoded by the mitochondrial genome and synthesized by the mitochondrial ribosome (mitoribosome). As a result, an appropriate regulation of mitochondrial protein synthesis is absolutely required to achieve and maintain normal mitochondrial function. Regarding miRNAs in mitochondria, it is well-recognized nowadays that several cellular mechanisms involving mitochondria are regulated by many genetic players that originate from either nuclear- or mitochondrial-encoded small noncoding RNAs (sncRNAs). Growing evidence collected from whole genome and transcriptome sequencing highlight the role of distinct members of this class, from short interfering RNAs (siRNAs) to miRNAs and long noncoding RNAs (lncRNAs). Some of the mechanisms that have been shown to be modulated are the expression of mitochondrial proteins itself, as well as the more complex coordination of mitochondrial structure and dynamics with its function. We devote particular attention to the role of mitochondrial miRNAs and to their role in the modulation of several molecular processes that could ultimately contribute to tissue regeneration accomplishment.


2008 ◽  
Vol 228 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Takafumi Ochi ◽  
Kayoko Kita ◽  
Toshihide Suzuki ◽  
Alice Rumpler ◽  
Walter Goessler ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Luíza Silva Rocha ◽  
Josilene Ramos Pinheiro ◽  
Thamilin Costa Nakamura ◽  
José Domingos Santos da Silva ◽  
Beatriz Gonçalves Silva Rocha ◽  
...  

AbstractIt is not clear if COVID-19 can be indirectly transmitted. It is not possible to conclude the role of the environment in transmission of SARS-CoV-2 without studying areas in which people transit in great numbers. In this work we aimed to better understand the role of environment in the spread of COVID-19. We investigated the presence of SARS-CoV-2 in fomites as well as in the air and in the sewage using RT-qPCR. We studied both, a reference market area and a COVID-19 reference hospital at Barreiras city, Brazil. We collected and analyzed a total of 418 samples from mask fronts, cell phones, paper money, card machines, sewage, air and bedding during the ascendant phase of the epidemiological curve of COVID-19 in Barreiras. As a result, we detected the human RNAse P gene in most of samples, which indicates the presence of human cells or their fragments in specimens. However, we did not detect any trace of SARS-CoV-2 in all samples analyzed. We conclude that, so far, the environment and inanimate materials did not have an important role in COVID-19 transmission in Barreiras city. Therefore, similar results can probably be found in other cities, mainly those with COVID-19 epidemiological scenarios similar to that of Barreiras city. Our study is a small piece indicating the possibility that fomites and the environment do not have an important role in COVID-19 transmission. However, further studies are necessary to better understand the world scenario.


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