Abstract
Previous evidence indicates that a number of proteins are able to interact with cognate mRNAs. These autogenous associations represent important regulatory mechanisms that control gene expression at the translational level. Using the catRAPID approach to predict the propensity of proteins to bind to RNA, we investigated the occurrence of autogenous associations in the human proteome. Our algorithm correctly identified binding sites in well-known cases such as thymidylate synthase, tumor suppressor P53, synaptotagmin-1, serine/ariginine-rich splicing factor 2, heat shock 70 kDa, ribonucleic particle-specific U1A and ribosomal protein S13. In addition, we found that several other proteins are able to bind to their own mRNAs. A large-scale analysis of biological pathways revealed that aggregation-prone and structurally disordered proteins have the highest propensity to interact with cognate RNAs. These findings are substantiated by experimental evidence on amyloidogenic proteins such as TAR DNA-binding protein 43 and fragile X mental retardation protein. Among the amyloidogenic proteins, we predicted that Parkinson’s disease-related α-synuclein is highly prone to interact with cognate transcripts, which suggests the existence of RNA-dependent factors in its function and dysfunction. Indeed, as aggregation is intrinsically concentration dependent, it is possible that autogenous interactions play a crucial role in controlling protein homeostasis.
Highlights
Proteins are involved in almost every cellular process, increasing evidence indicates that coding and non-coding RNAs play fundamental roles in gene regulation [1,2] and disease [3,4]
We found that tumor suppressor p53, involved in the two top-enriched pathways ‘Signaling events mediated by HDAC Class III’ and ‘Hypoxic and oxygen homeostasis regulation of HIF-1-alpha’, is able to bind to its own mRNA [17,39,40]
In a number of biological pathways annotated in Reactome and NCI-PID, we found enrichment for autogenous interactions
Summary
Proteins are involved in almost every cellular process, increasing evidence indicates that coding and non-coding RNAs play fundamental roles in gene regulation [1,2] and disease [3,4]. Previous studies suggested that ribonucleoprotein interactions might be able to facilitate protein and RNA folding [9,10]. TAR DNA-binding protein 43 (TDP-43) and Fragile X Mental Retardation protein (FMRP) have been found to interact with their own mRNAs [15,16]. In these cases, expression is regulated by a negative feedback loop involving the 30 untranslated region (UTR). Structurally disordered proteins such as Serine/Arginine-rich splicing factor 2 (SRSF2) [19] as well as heterogeneous ribonucleoprotein
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