Abstract:
:Mutations in genes that encode tRNAs, aminoacyl-tRNA syntheases, tRNA modifying enzymes and other tRNA interacting partners are associated with neuropathies, cancer, type-II diabetes and hearing loss, but how these mutations cause disease is unclear. We have hypothesized that levels of tRNA decoding error (mistranslation) that do not fully impair embryonic development can accelerate cell degeneration through proteome instability and saturation of the proteostasis network. To test this hypothesis we have induced mistranslation in zebrafish embryos using mutant tRNAs that misincorporate Serine (Ser) at various non-cognate codon sites. Embryo viability was affected and malformations were observed, but a significant proportion of embryos survived by activating the unfolded protein response (UPR), the ubiquitin proteasome pathway (UPP) and downregulating protein biosynthesis. Accumulation of reactive oxygen species (ROS), mitochondrial and nuclear DNA damage and disruption of the mitochondrial network, were also observed, suggesting that mistranslation had a strong negative impact on protein synthesis rate, ER and mitochondrial homeostasis. We postulate that mistranslation promotes gradual cellular degeneration and disease through protein aggregation, mitochondrial dysfunction and genome instability.
journal_name
RNA Bioljournal_title
RNA biologyauthors
Reverendo M,Soares AR,Pereira PM,Carreto L,Ferreira V,Gatti E,Pierre P,Moura GR,Santos MAdoi
10.4161/rna.32199subject
Has Abstractpub_date
2014-01-01 00:00:00pages
1199-213issue
9eissn
1547-6286issn
1555-8584journal_volume
11pub_type
杂志文章相关文献
RNA Biology文献大全abstract::Prokaryotes immunize themselves against transmissible genetic elements by the integration (acquisition) in clustered regularly interspaced short palindromic repeats (CRISPR) loci of spacers homologous to invader nucleic acids, defined as protospacers. Following acquisition, mono-spacer CRISPR RNAs (termed crRNAs) guid...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.24023
更新日期:2013-05-01 00:00:00
abstract::Deinococcus radiodurans is a highly stress resistant bacterium that encodes universal as well as lineage-specific factors involved in DNA transcription and repair. However, the effects of DNA lesions on RNA synthesis by D. radiodurans RNA polymerase (RNAP) have never been studied. We investigated the ability of this R...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1656027
更新日期:2019-12-01 00:00:00
abstract::Termination of RNA polymerase II (RNAPII) transcription is a fundamental step of gene expression that involves the release of the nascent transcript and dissociation of RNAPII from the DNA template. As transcription termination is intimately linked to RNA 3' end processing, termination pathways have a key decisive inf...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.1080/15476286.2015.1073433
更新日期:2015-01-01 00:00:00
abstract::The human genome encodes several thousand long non-protein coding transcripts>200 nucleotides in length, a subset of which were shown to play important roles in regulation of gene expression. We recently identified TINCR, a lncRNA required for induction of key differentiation genes in epidermal tissue, including genes...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.26249
更新日期:2013-10-01 00:00:00
abstract::The innate immune system is the frontline host protection against pathogens. Effective antiviral immunity is elicited upon recognition of viral RNAs by the host pattern recognition receptors. One of the major viral RNA sensors is retinoic acid inducible gene-1, which triggers the production of interferons (IFNs). In t...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1624471
更新日期:2019-09-01 00:00:00
abstract::MicroRNAs (miRNAs) are key regulators of gene expression and play critical roles in modulating metabolism, development and physiology in animals and plants. miRNA levels are transcriptionally and post-transcriptionally controlled for their proper function. Recent studies have shown that RNA-binding proteins play impor...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.22740
更新日期:2012-12-01 00:00:00
abstract::Pentatricopeptide repeat (PPR) proteins control diverse aspects of RNA metabolism across the eukaryotic domain. Recent computational and structural studies have provided new insights into how they recognize RNA, and show that the recognition is sequence-specific and modular. The modular code for RNA-binding by PPR pro...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.24769
更新日期:2013-01-01 00:00:00
abstract::All organisms must keep their DNA intact and free of lesions to obtain faithful transmission of genetic information, and many cellular proteins are involved in genome maintenance. However, also other macromolecules may be subject to repair. Deleterious lesions in proteins can be reversed by several mechanisms, and thi...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.2.1.1602
更新日期:2005-01-01 00:00:00
abstract::RNA exosomes are large multi-subunit protein complexes involved in controlled and processive 3' to 5' RNA degradation. Exosomes form large molecular chambers and harbor multiple nuclease sites as well as RNA binding regions. This makes a quantitative kinetic analysis of RNA degradation with reliable parameter and erro...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.8.1.14067
更新日期:2011-01-01 00:00:00
abstract::How have the branchpoint motifs evolved in organisms of different complexity? Here we identified and examined the consensus motifs (R1C2T3R4A5Y6, R: A or G, Y: C or T) of 898 fungal genomes. In Ascomycota unicellular yeasts, the G4/A4 ratio is mostly (98%) below 0.125 but increases sharply in multicellular species by ...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1697548
更新日期:2020-03-01 00:00:00
abstract::The muscle specific miRNA, miR-206, is important for the process of myogenesis; however, studying the function of miR-206 in muscle development and differentiation still proves challenging because the complement of mRNA targets it regulates remains undefined. In addition, miR-206 shares close sequence similarity to mi...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1737443
更新日期:2020-07-01 00:00:00
abstract::RNA editing in flowering plant mitochondria targets several hundred C nucleotides mostly in mRNAs to be altered to U. Several nuclear encoded genes have been recently identified predominantly in Arabidopsis thaliana which code for proteins involved in specific RNA editing events in plastids or mitochondria. These nucl...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.8.1.14298
更新日期:2011-01-01 00:00:00
abstract::Two different isolates of the myxomycete Didymium iridis harbour homing endonuclease genes that are expressed from group I introns inserted into identical sites within the small subunit ribosomal DNA. The homing endonuclease proteins are related in sequence, and their gene structures share similar features such as the...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.3.4.3958
更新日期:2006-10-01 00:00:00
abstract::Studies on the regulation of gene expression in eukaryotes in the past 20 years have consistently revealed increasing levels of complexity. Thirty years ago it seemed that we had understood the basic principles of gene regulation in eukaryotes. It was thought that regulation of transcription was the first and most imp...
journal_title:RNA biology
pub_type:
doi:10.4161/rna.28037
更新日期:2014-01-01 00:00:00
abstract::Alternative splicing (AS) plays a central role during cell-fate determination. However, how the core spliceosomal factors (CSFs) are involved in this process is poorly understood. Here, we report the down-regulation of the U2AF1 CSF during stem cell differentiation. To investigate its function in stemness and differen...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1733800
更新日期:2020-06-01 00:00:00
abstract::Eukaryotic gene expression must be coordinated for the proper functioning of biological processes. This coordination can be achieved both at the transcriptional and post-transcriptional levels. In both cases, regulatory sequences placed at either promoter regions or on UTRs function as markers recognized by regulators...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.7116
更新日期:2008-10-01 00:00:00
abstract::Alzheimer's disease (AD) has devastating consequences for patients during its slow, progressive course. It is important to understand the pathology of AD onset. Recently, circular RNAs (circRNAs) have been found to participate in many human diseases including cancers and neurodegenerative conditions. In this study, we...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1783487
更新日期:2020-12-01 00:00:00
abstract::Oncogenic viruses are associated with approximately 15% of human cancers. In viral infections, microRNAs play an important role in host-pathogen interactions. miR-21 is a highly conserved non-coding RNA that not only regulates the development of oncogenic viral diseases, but also responds to the regulation of intracel...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2021.1880756
更新日期:2021-01-27 00:00:00
abstract::The protein domain arrangement known as the La-module, comprised of a La motif (LaM) followed by a linker and RNA recognition motif (RRM), is found in seven La-related proteins: LARP1, LARP1B, LARP3 (La protein), LARP4, LARP4B, LARP6, and LARP7 in humans. Several LARPs have been characterized for their distinct activi...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2020.1860376
更新日期:2020-12-23 00:00:00
abstract::The RIG-I-like receptors (RLRs)--RIG-I, MDA5, and LGP2--detect intracellular pathogenic RNA and elicit an antiviral immune response during viral infection. The protein architecture of the RLR family consists of multiple functional domains, including N-terminal Caspase Activation and Recruitment Domains (CARDs) for sig...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.27717
更新日期:2014-01-01 00:00:00
abstract::Genuine La and La-related proteins group 7 (LARP7) bind to the non-coding RNAs transcribed by RNA polymerase III (RNAPIII), which end in UUU-3'OH. The La motif and RRM1 of these proteins (the La module) cooperate to bind the UUU-3'OH, protecting the RNA from degradation, while other domains may be important for RNA fo...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.23608
更新日期:2013-03-01 00:00:00
abstract::Circular RNAs (circRNAs) constitute a large class of RNA species formed by the back-splicing of co-linear exons, often within protein-coding transcripts. Despite much progress in the field, it remains elusive whether the majority of circRNAs are merely aberrant splicing by-products with unknown functions, or their pro...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2016.1207036
更新日期:2016-09-01 00:00:00
abstract::Ribosome biogenesis is an essential process initiated in the nucleolus. In eukaryotes, multiple ribosome biogenesis factors (RBFs) can be found in the nucleolus, the nucleus and in the cytoplasm. They act in processing, folding and modification of the pre-ribosomal (r)RNAs, incorporation of ribosomal proteins (RPs), e...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2016.1154252
更新日期:2016-01-01 00:00:00
abstract::Population bottlenecks often cause strong reductions in genetic diversity and alter population structure. In the context of host-parasite interactions, bottlenecks could in theory benefit either the host or the pathogen. We predicted that bottlenecking of bacterial populations that evolve CRISPR immunity against bacte...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2019.1578608
更新日期:2019-04-01 00:00:00
abstract::The universal genetic code is a translation table by which nucleic acid sequences can be interpreted as polypeptides with a wide range of biological functions. That information is used by aminoacyl-tRNA synthetases to translate the code. Moreover, amino acid properties dictate protein folding. We recently reported tha...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2015.1112488
更新日期:2016-01-01 00:00:00
abstract::The quaking viable (qk(v)) mice have attracted attention because of their characteristic tremor caused by their dysmyelination. In the central nervous system, qk(v) mice fail to develop mature myelinating oligodendrocytes and display uncompacted myelin. The genetic defect in the qk(v) mice prevents the proper expressi...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.2.2.1603
更新日期:2005-04-01 00:00:00
abstract::Epstein-Barr virus (EBV) was the first human cancer-causing virus to be discovered over fifty years ago. Given its relatively large genome size for a virus and hence the capacity to store more than mere protein-coding information, EBV also harbours genetic material for producing an array of distinct noncoding (nc)RNAs...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2021.1875184
更新日期:2021-01-30 00:00:00
abstract::Single-stranded oligonucleotides (ssOligos) are efficiently taken up by living cells without the use of transfection reagents. This phenomenon called 'gymnosis' enables the sequence-specific silencing of target genes in various types of cells. Several antisense ssOligos are used for the treatment of human diseases. Ho...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.1080/15476286.2017.1302641
更新日期:2017-11-02 00:00:00
abstract::The signal recognition particle (SRP) is a ribonucleoprotein complex which participates in the targeting of protein to cellular membranes. The RNA component of the SRP has been found in all domains of life, but the size of the molecule and the number of RNA secondary structure elements vary considerably between the di...
journal_title:RNA biology
pub_type: 杂志文章
doi:10.4161/rna.6.5.9753
更新日期:2009-11-01 00:00:00
abstract::Alternative splicing (AS) of pre-messenger RNAs is a major process contributing to both transcriptome and proteome diversity in various physiological and pathological situations. There is also accumulating evidence that various stresses impact on AS. In particular, recent analyses of the transcriptome reveal large num...
journal_title:RNA biology
pub_type: 杂志文章,评审
doi:10.4161/rna.8.5.16016
更新日期:2011-09-01 00:00:00