Switching of cardiac troponin I between nuclear and cytoplasmic localization during muscle differentiation

Kharitonov, Alexey V.; Shubina, Maria Y.; Nosov, G. A.; Mamontova, Anastasia V.; Arifulin, Eugene A.; Lisitsyna, Olga M.; Налобин, Д. С.; Musinova, Yana R.; Sheval, Eugene V.

doi:10.1016/j.bbamcr.2019.118601

“…Sequences similar or identical to eukaryotic NLSs are present in proteins in different prokaryotes (Rossi et al 1993;Nederlof et al 1995;Perić et al 2008;Lee et al 2012;Moon et al 2012;Kim et al 2016;Kwon et al 2016;Lisitsyna et al 2020;Melnikov et al 2020), indicating that the origin of NLSs precedes the separation of the nucleus and the cytoplasm. This integration of NLS(s) into different (mostly DNA-and/or RNA-binding) domains was also observed in modern Eukaryota (LaCasse and Lefebvre 1995;Cokol et al 2000;Melnikov et al 2015;Kharitonov et al 2020;Lisitsyna et al 2020).…”

Section: Introductionsupporting

confidence: 66%

Molecular Coevolution of Nuclear and Nucleolar Localization Signals inside the Basic Domain of HIV-1 Tat

Kurnaeva

¹

,

Zalevsky

²

,

Arifulin

³

et al. 2022

J Virol

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During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses. IMPORTANCE Here, we investigated the molecular mechanism of NLS and NoLS integration into the basic domain of HIV-1 Tat ( 49 RKKRRQRRR 57 ), and found that these two supplementary functions (i.e., function of NLS and NoLS) are embedded in the basic domain amino acid sequence. The integration of NLSs and NoLSs into functional domains of viral proteins enriched with positively charged amino acids is a mechanism that allows the concentration of different functions within small protein regions. Integration of NLS and NoLS into functional protein domains might have influenced the viral evolution, as this could prevent an increase in the protein size.

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“…Sequences similar or identical to eukaryotic NLSs are present in proteins in different prokaryotes (Rossi et al 1993;Nederlof et al 1995;Perić et al 2008;Lee et al 2012;Moon et al 2012;Kim et al 2016;Kwon et al 2016;Lisitsyna et al 2020;Melnikov et al 2020), indicating that the origin of NLSs precedes the separation of the nucleus and the cytoplasm. This integration of NLS(s) into different (mostly DNA-and/or RNA-binding) domains was also observed in modern Eukaryota (LaCasse and Lefebvre 1995; Cokol et al 2000;Melnikov et al 2015;Kharitonov et al 2020;Lisitsyna et al 2020).…”

Section: Introductionsupporting

confidence: 64%

“…Sequences similar or identical to eukaryotic NLSs are present in proteins in different prokaryotes (4)(5)(6)(7)(8)(9)(10)(11)(12), indicating that the origin of NLSs precedes the separation of the nucleus and the cytoplasm. This integration of NLS(s) into different (mostly DNA-and/or RNA-binding) domains was also observed in modern Eukaryota (11,(13)(14)(15)(16).…”

supporting

confidence: 66%

Molecular coevolution of nuclear and nucleolar localization signals inside basic domain of HIV-1 Tat

Kurnaeva¹,

Zalevsky

²

,

Arifulin³

et al. 2021

Preprint

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0

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During evolution, viruses had to adapt to an increasingly complex environment of eukaryotic cells. Viral proteins that need to enter the cell nucleus or associate with nucleoli possess nuclear localization signals (NLSs) and nucleolar localization signals (NoLSs) for nuclear and nucleolar accumulation, respectively. As viral proteins are relatively small, acquisition of novel sequences seems to be a more complicated task for viruses than for eukaryotes. Here, we carried out a comprehensive analysis of the basic domain (BD) of HIV-1 Tat to show how viral proteins might evolve with NLSs and NoLSs without an increase in protein size. The HIV-1 Tat BD is involved in several functions, the most important being the transactivation of viral transcription. The BD also functions as an NLS, although it is substantially longer than a typical NLS. It seems that different regions in the BD could function as NLSs due to its enrichment with positively charged amino acids. Additionally, the high positive net charge inevitably causes the BD to function as an NoLS through a charge-specific mechanism. The integration of NLSs and NoLSs into functional domains enriched with positively charged amino acids might be a mechanism that allows the condensation of different functional sequences in small protein regions and, as a result, to reduce protein size, influencing the origin and evolution of NLSs and NoLSs in viruses.

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“…Interestingly, sequences that are similar to NLS can also be predicted and experimentally defined as being present in some cytoplasmic proteins of modern organisms. This indicates that during evolution, some proteins, albeit possibly resident inside nuclei due to the presence of an integrated NLS, were excluded from the nucleus via different mechanisms, as discussed elsewhere [28]".…”

Section: Reviewer Commentsmentioning

confidence: 79%

Origin of the nuclear proteome on the basis of pre-existing nuclear localization signals in prokaryotic proteins

Lisitsyna

¹

,

Kurnaeva

²

,

Arifulin

³

et al. 2020

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Background: The origin of the selective nuclear protein import machinery, which consists of nuclear pore complexes and adaptor molecules interacting with the nuclear localization signals (NLSs) of cargo molecules, is one of the most important events in the evolution of eukaryotic cells. How proteins were selected for import into the forming nucleus remains an open question. Results: Here, we demonstrate that functional NLSs may be integrated in the nucleotide-binding domains of both eukaryotic and prokaryotic proteins and may coevolve with these domains. Conclusion: The presence of sequences similar to NLSs in the DNA-binding domains of prokaryotic proteins might have created an advantage for nuclear accumulation of these proteins during evolution of the nuclear-cytoplasmic barrier, influencing which proteins accumulated and became compartmentalized inside the forming nucleus (i.e., the content of the nuclear proteome). Reviewers: This article was reviewed by Sergey Melnikov and Igor Rogozin. Open peer review: Reviewed by Sergey Melnikov and Igor Rogozin. For the full reviews, please go to the Reviewers' comments section.

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Switching of cardiac troponin I between nuclear and cytoplasmic localization during muscle differentiation

Cited by 6 publications

References 42 publications

Molecular Coevolution of Nuclear and Nucleolar Localization Signals inside the Basic Domain of HIV-1 Tat

Molecular Coevolution of Nuclear and Nucleolar Localization Signals inside the Basic Domain of HIV-1 Tat

Molecular coevolution of nuclear and nucleolar localization signals inside basic domain of HIV-1 Tat

Origin of the nuclear proteome on the basis of pre-existing nuclear localization signals in prokaryotic proteins

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