eprintid: 34811
rev_number: 22
eprint_status: archive
userid: 8067
dir: disk0/00/03/48/11
datestamp: 2024-05-14 08:39:19
lastmod: 2024-05-27 16:59:30
status_changed: 2024-05-14 08:39:19
type: doctoralThesis
metadata_visibility: show
creators_name: Wassmer, Elsa
title: What makes an RNA-binding protein (RBP):
exploring the RNA-binding domains (RBDs) of experimentally
detected RBPs
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
abstract: RNA-binding proteins, or RBPs, are responsible for the regulation of RNA fate from
transcription to decay. In the past 20 years, their implications in human pathology have been highlighted, especially in hereditary neurodegenerative diseases but also in the development of cancer. Furthermore, in recent studies, the emergence of long non-coding RNAs (lncRNAs) questioned the established dogma and showed that RNAs can also influence the fate of RBPs, through the regulation of their localization, interactions, or activation. Therefore, it became urgent to systematically detect the proteins able to bind to RNA, and several different techniques have been developed in the past ten years to address this challenge. However, the accumulation of published lists of RBPs toughened the access to comprehensive data. Subsequently, the RBP2GO database was created. This database compiles all of the proteome wide screens available in the literature, and facilitate the access of scientists to this evergrowing mass of information. 
The multiplicity of proteome-wide RBP screens also brings into question the specificity of the published data. Indeed, the number of RBPs in human has quickly risen up to a third of the total proteome, and little overlap can be found between the different datasets. Furthermore, most of the techniques employed do not allow the identification of the precise part of the protein which is binding RNA. As a result, no information on RNA-binding features was available for the RBPs of the RBP2GO database. Hence, I exploited the data available in this database to
study the presence of RNA-binding domains in experimentally detected RBPs. The aim of this analysis was to determine if these domains could be used to better segregate relevant RBP candidates. I first compiled a list of RNA-binding domains (RBDs), and selected them based on their enrichment in RBPs to then dissect their repartition on the proteins of the database. The same was done for RNA-related family IDs (Rfam IDs), as well as disordered regions. This bioinformatic analysis showed that RBDs and Rfam IDs are strong indicators of the RNAbinding
potential of proteins. However, the presence of disorder did not appear as important, and a higher proportion of disorder was observed in the proteins already exhibiting an RBD. This gained knowledge was used to predict new RBP candidates. The RBPs with no RBD were also studied, and 15 new RBDs were predicted and subsequently validated using RNA-binding peptides from mass spectrometry data. Finally, a new score, called the RBP2GO composite
score, was created as a single metric assembling both experimental RBPome data and the presence of RBDs or Rfam IDs. This score was used to then compile a list of high-confidence human RNA-binding proteins. All of this newly acquired information was integrated into the RBP2GO database (https://RBP2GO.dkfz.de), to provide an easy access to future users.
date: 2024
id_scheme: DOI
id_number: 10.11588/heidok.00034811
ppn_swb: 1889956082
own_urn: urn:nbn:de:bsz:16-heidok-348116
date_accepted: 2023-12-15
advisor: HASH(0x56009aa8b358)
language: eng
bibsort: WASSMERELSWHATMAKESA
full_text_status: public
place_of_pub: Heidelberg
citation:   Wassmer, Elsa  (2024) What makes an RNA-binding protein (RBP): exploring the RNA-binding domains (RBDs) of experimentally detected RBPs.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/9/230719_thesis_final.pdf
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/2/Table_1.xlsx
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/3/Table_5.xlsx
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/4/Table_6.xlsx
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/5/Table_7.xlsx
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/6/Table_8.xlsx
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/7/Table_10.xlsx
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34811/8/Table_12.xlsx