The role of the protein-RNA recognition code in neurodegeneration.

The role of the protein-RNA recognition code in neurodegeneration.

Publication date: Apr 12, 2019

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.

Nahalka, J. The role of the protein-RNA recognition code in neurodegeneration. 20453. 2019 Cell Mol Life Sci.

Concepts Keywords
Amino Acid Neurodegeneration
Amyloid Transmissible spongiform encephalopathy
Amyotrophic Lateral Sclerosis MicroRNA
BLAST Proteins
Endogenous Prion
Foci Genetics
Genome Amyloidosis
MicroRNA Gene expression
MicroRNAs RNA
MRNAs Branches of biology
Myotonic Dystrophy
Neurodegeneration
Neurodegenerative Disorders
Nucleotide
Nucleotides
Peptide
Prion
Protein
RNA
Sci
Toxicity
Transcription

Semantics

Type Source Name
pathway BSID Prion diseases
disease MESH prion diseases
gene UNIPROT PTPN5
gene UNIPROT COL23A1
gene UNIPROT WDR33
gene UNIPROT SYPL2
gene UNIPROT MESP2
gene UNIPROT REM2
gene UNIPROT PTCD3
gene UNIPROT CD48
disease MESH myotonic dystrophy
disease DOID amyotrophic lateral sclerosis
gene UNIPROT SFPQ
disease MESH amyotrophic lateral sclerosis
gene UNIPROT HNRNPDL
gene UNIPROT HNRNPC
disease MESH neurodegenerative disorders
disease MESH repression
gene UNIPROT SLC35G1

Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *