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The role of the protein-RNA recognition code in neurodegeneration.
Cell Mol Life Sci. 2019 Jun; 76(11):2043-2058.CM

Abstract

MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post-translational riboregulation. This conceptual review explores the literature on neurodegenerative disorders. Research on the association between neurodegeneration and RNA-repeat toxicity provides data that support a protein-RNA recognition code. For example, this code explains why hnRNP H and SFPQ proteins, which are involved in amyotrophic lateral sclerosis, are sequestered by the (GGGGCC)n repeat sequence. Similarly, it explains why MNBL proteins and (CTG)n repeats in RNA, which are involved in myotonic dystrophy, are sequestered into RNA foci. Using this code, proteins involved in diseases can be identified. A simple protein BLAST search of the human genome for amino acid repeats that correspond to the nucleotide repeats reveals new proteins among already known proteins that are involved in diseases. For example, the (CAG)n repeat sequence, when transcribed into possible peptide sequences, leads to the identification of PTCD3, Rem2, MESP2, SYPL2, WDR33, COL23A1, and others. After confirming this approach on RNA repeats, in the next step, the code was used in the opposite manner. Proteins that are involved in diseases were compared with microRNAs involved in those diseases. For example, a reasonable correspondence of microRNA 9 and 107 with amyloid-β-peptide (Aβ42) was identified. In the last step, a miRBase search for micro-nucleotides, obtained by transcription of a prion amino acid sequence, revealed new microRNAs and microRNAs that have previously been identified as involved in prion diseases. This concept provides a useful key for designing RNA or peptide probes.

Authors+Show Affiliations

Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dubravska cesta 9, 84538, Bratislava, Slovak Republic. nahalka@savba.sk. Institute of Chemistry, Centre of Excellence for White-green Biotechnology, Slovak Academy of Sciences, Trieda Andreja Hlinku 2, 94976, Nitra, Slovak Republic. nahalka@savba.sk.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

30980111

Citation

Nahalka, Jozef. "The Role of the protein-RNA Recognition Code in Neurodegeneration." Cellular and Molecular Life Sciences : CMLS, vol. 76, no. 11, 2019, pp. 2043-2058.
Nahalka J. The role of the protein-RNA recognition code in neurodegeneration. Cell Mol Life Sci. 2019;76(11):2043-2058.
Nahalka, J. (2019). The role of the protein-RNA recognition code in neurodegeneration. Cellular and Molecular Life Sciences : CMLS, 76(11), 2043-2058. https://doi.org/10.1007/s00018-019-03096-3
Nahalka J. The Role of the protein-RNA Recognition Code in Neurodegeneration. Cell Mol Life Sci. 2019;76(11):2043-2058. PubMed PMID: 30980111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of the protein-RNA recognition code in neurodegeneration. A1 - Nahalka,Jozef, Y1 - 2019/04/12/ PY - 2019/01/02/received PY - 2019/04/08/accepted PY - 2019/03/14/revised PY - 2019/4/14/pubmed PY - 2019/5/21/medline PY - 2019/4/14/entrez KW - Alzheimer’s disease KW - Huntington’s disease KW - Molecular recognition KW - Non-coding RNA KW - Parkinson’s disease KW - Prion diseases SP - 2043 EP - 2058 JF - Cellular and molecular life sciences : CMLS JO - Cell. Mol. Life Sci. VL - 76 IS - 11 N2 - MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post-translational riboregulation. This conceptual review explores the literature on neurodegenerative disorders. Research on the association between neurodegeneration and RNA-repeat toxicity provides data that support a protein-RNA recognition code. For example, this code explains why hnRNP H and SFPQ proteins, which are involved in amyotrophic lateral sclerosis, are sequestered by the (GGGGCC)n repeat sequence. Similarly, it explains why MNBL proteins and (CTG)n repeats in RNA, which are involved in myotonic dystrophy, are sequestered into RNA foci. Using this code, proteins involved in diseases can be identified. A simple protein BLAST search of the human genome for amino acid repeats that correspond to the nucleotide repeats reveals new proteins among already known proteins that are involved in diseases. For example, the (CAG)n repeat sequence, when transcribed into possible peptide sequences, leads to the identification of PTCD3, Rem2, MESP2, SYPL2, WDR33, COL23A1, and others. After confirming this approach on RNA repeats, in the next step, the code was used in the opposite manner. Proteins that are involved in diseases were compared with microRNAs involved in those diseases. For example, a reasonable correspondence of microRNA 9 and 107 with amyloid-β-peptide (Aβ42) was identified. In the last step, a miRBase search for micro-nucleotides, obtained by transcription of a prion amino acid sequence, revealed new microRNAs and microRNAs that have previously been identified as involved in prion diseases. This concept provides a useful key for designing RNA or peptide probes. SN - 1420-9071 UR - https://www.unboundmedicine.com/medline/citation/30980111/The_role_of_the_protein_RNA_recognition_code_in_neurodegeneration_ L2 - https://dx.doi.org/10.1007/s00018-019-03096-3 DB - PRIME DP - Unbound Medicine ER -