Comparative Genomics Reveals Long, Evolutionarily Conserved, Low-Complexity Islands in Yeast Proteins

2006 ◽  
Vol 63 (3) ◽  
pp. 415-425 ◽  
Author(s):  
Philip A. Romov ◽  
Fubin Li ◽  
Peter N. Lipke ◽  
Susan L. Epstein ◽  
Wei-Gang Qiu
2020 ◽  
Vol 118 (3) ◽  
pp. 6a
Author(s):  
Erik W. Martin ◽  
Alex S. Holehouse ◽  
Ivan Peran ◽  
Jeremias Incicco ◽  
Andrea Soranno ◽  
...  

2019 ◽  
Author(s):  
Yi Lin ◽  
Xiaoming Zhou ◽  
Masato Kato ◽  
Daifei Liu ◽  
Sina Ghaemmaghami ◽  
...  

SummaryAn evolutionarily conserved low complexity (LC) domain is found within a 152 residue segment localized to the carboxyl-terminal region of the TDP43 RNA-binding protein. This TDP43 LC domain contains ten conserved methionine residues. Self-association of this domain leads to the formation of liquid-like droplets composed of labile, cross-β polymers. Exposure of polymers to low concentrations of H2O2 leads to a phenomenon of droplet melting that can be reversed upon exposure of the oxidized protein to the MsrA and MsrB methionine sulfoxide reductase enzymes, thioredoxin, thioredoxin reductase and NADPH. Morphological features of the cross-β polymers were revealed by a method of H2O2-mediated footprinting. Similar TDP43 LC domain footprints were observed in highly polymerized, hydrogel samples, liquid-like droplet samples, and living cells. The ability of H2O2 to impede cross-β polymerization was abrogated by a prominent ALS-causing mutation that changes methionine residue 337 to valine. These observations offer potentially useful insight into the biological role of TDP43 in facilitating synapse-localized translation, as well as aberrant aggregation of the protein in neurodegenerative disease.


Author(s):  
Roman Ochsenreiter ◽  
Ivo L. Hofacker ◽  
Michael T. Wolfinger

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3'UTR of tick-borne, insect-specific and no-known-vector flaviviruses in silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs xrRNAs within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3'UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs


2019 ◽  
Author(s):  
Adriano de Bernardi Schneider ◽  
Roman Ochsenreiter ◽  
Reilly Hostager ◽  
Ivo L. Hofacker ◽  
Daniel Janies ◽  
...  

AbstractChikungunya virus (CHIKV), a mosquito-borne alphavirus of the family Togaviridae, has recently emerged in the Americas from lineages from two continents, Asia and Africa. Historically, CHIKV circulated as at least four lineages worldwide with both enzootic and epidemic transmission cycles. To understand the recent patterns of emergence and the current status of the CHIKV spread, updated analyses of the viral genetic data and metadata are needed. Here, we performed phylogenetic and comparative genomics screens of CHIKV genomes, taking advantage of the public availability of many recently sequenced isolates. Based on these new data and analyses, we derive a revised phylogeny from nucleotide sequences in coding regions. Using this phylogeny, we uncover the presence of several distinct lineages in Africa that were previously considered a single one. In parallel, we performed thermodynamic modeling of CHIKV untranslated regions (UTRs), which revealed evolutionarily conserved structured and unstructured RNA elements in the 3’UTR. We provide evidence for duplication events in recently emerged American isolates of the Asian CHIKV lineage and propose the existence of a flexible 3’UTR architecture among different CHIKV lineages.


2020 ◽  
Vol 117 (46) ◽  
pp. 28727-28734
Author(s):  
Yi Lin ◽  
Xiaoming Zhou ◽  
Masato Kato ◽  
Daifei Liu ◽  
Sina Ghaemmaghami ◽  
...  

A methionine-rich low complexity (LC) domain is found within a C-terminal region of the TDP43 RNA-binding protein. Self-association of this domain leads to the formation of labile cross-β polymers and liquid-like droplets. Treatment with H2O2caused phenomena of methionine oxidation and droplet melting that were reversed upon exposure of the oxidized protein to methionine sulfoxide reductase enzymes. Morphological features of the cross-β polymers were revealed by H2O2-mediated footprinting. Equivalent TDP43 LC domain footprints were observed in polymerized hydrogels, liquid-like droplets, and living cells. The ability of H2O2to impede cross-β polymerization was abrogated by the prominent M337V amyotrophic lateral sclerosis-causing mutation. These observations may offer insight into the biological role of TDP43 in facilitating synapse-localized translation as well as aberrant aggregation of the protein in neurodegenerative diseases.


Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 798 ◽  
Author(s):  
Adriano de Bernardi Schneider ◽  
Roman Ochsenreiter ◽  
Reilly Hostager ◽  
Ivo L. Hofacker ◽  
Daniel Janies ◽  
...  

Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the family Togaviridae, has recently emerged in the Americas from lineages from two continents: Asia and Africa. Historically, CHIKV circulated as at least four lineages worldwide with both enzootic and epidemic transmission cycles. To understand the recent patterns of emergence and the current status of the CHIKV spread, updated analyses of the viral genetic data and metadata are needed. Here, we performed phylogenetic and comparative genomics screens of CHIKV genomes, taking advantage of the public availability of many recently sequenced isolates. Based on these new data and analyses, we derive a revised phylogeny from nucleotide sequences in coding regions. Using this phylogeny, we uncover the presence of several distinct lineages in Africa that were previously considered a single one. In parallel, we performed thermodynamic modeling of CHIKV untranslated regions (UTRs), which revealed evolutionarily conserved structured and unstructured RNA elements in the 3’UTR. We provide evidence for duplication events in recently emerged American isolates of the Asian CHIKV lineage and propose the existence of a flexible 3’UTR architecture among different CHIKV lineages.


2021 ◽  
Author(s):  
Rory J Craig ◽  
Ahmed R Hasan ◽  
Rob W Ness ◽  
Peter D Keightley

Abstract Despite its role as a reference organism in the plant sciences, the green alga Chlamydomonas reinhardtii entirely lacks genomic resources from closely related species. We present highly contiguous and well-annotated genome assemblies for three unicellular C. reinhardtii relatives: Chlamydomonas incerta, Chlamydomonas schloesseri, and the more distantly related Edaphochlamys debaryana. The three Chlamydomonas genomes are highly syntenous with similar gene contents, although the 129.2 Mb C. incerta and 130.2 Mb C. schloesseri assemblies are more repeat-rich than the 111.1 Mb C. reinhardtii genome. We identify the major centromeric repeat in C. reinhardtii as a LINE transposable element homologous to Zepp (the centromeric repeat in Coccomyxa subellipsoidea) and infer that centromere locations and structure are likely conserved in C. incerta and C. schloesseri. We report extensive rearrangements, but limited gene turnover, between the minus mating type loci of these Chlamydomonas species. We produce an eight-species core-Reinhardtinia whole-genome alignment, which we use to identify several hundred false positive and missing genes in the C. reinhardtii annotation and >260,000 evolutionarily conserved elements in the C. reinhardtii genome. In summary, these resources will enable comparative genomics analyses for C. reinhardtii, significantly extending the analytical toolkit for this emerging model system.


2019 ◽  
Author(s):  
Roman Ochsenreiter ◽  
Ivo L. Hofacker ◽  
Michael T. Wolfinger

AbstractUntranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3’UTR of tick-borne, insect-specific and no-known-vector flavivirusesin silico. Our data support the wide distribution of previously experimentally characterized exoribonuclease resistant RNAs (xrRNAs) within tick-borne and no-known-vector flaviviruses and provide evidence for the existence of a cascade of duplicated RNA structures within insect-specific flaviviruses. On a broader scale, our findings indicate that viral 3’UTRs represent a flexible scaffold for evolution to come up with novel xrRNAs.


2021 ◽  
Vol 22 (4) ◽  
pp. 1727
Author(s):  
Kristina Kastano ◽  
Pablo Mier ◽  
Miguel A. Andrade-Navarro

Low complexity regions (LCRs) are very frequent in protein sequences, generally having a lower propensity to form structured domains and tending to be much less evolutionarily conserved than globular domains. Their higher abundance in eukaryotes and in species with more cellular types agrees with a growing number of reports on their function in protein interactions regulated by post-translational modifications. LCRs facilitate the increase of regulatory and network complexity required with the emergence of organisms with more complex tissue distribution and development. Although the low conservation and structural flexibility of LCRs complicate their study, evolutionary studies of proteins across species have been used to evaluate their significance and function. To investigate how to apply this evolutionary approach to the study of LCR function in protein–protein interactions, we performed a detailed analysis for Huntingtin (HTT), a large protein that is a hub for interaction with hundreds of proteins, has a variety of LCRs, and for which partial structural information (in complex with HAP40) is available. We hypothesize that proteins RASA1, SYN2, and KAT2B may compete with HAP40 for their attachment to the core of HTT using similar LCRs. Our results illustrate how evolution might favor the interplay of LCRs with domains, and the possibility of detecting multiple modes of LCR-mediated protein–protein interactions with a large hub such as HTT when enough protein interaction data is available.


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