Abstract
Heteregeneous ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that take part in all processes that involve mRNA maturation. As a consequence, alterations of their homeostasis may lead to many complex pathological disorders, such as neurodegeneration and cancer. For many of these proteins, however, their exact function and cellular targets are still not very well known. Here, we focused the attention on two hnRNP family members, hnRNP Q and hnRNP R, that we previously found affecting TDP-43 activity both in Drosophila melanogaster and human neuronal cell line. Classification of these two human proteins as paralogs is suported by the high level of sequence homology and by the observation that in fly they correspond to the same protein, namely Syp. We profiled differentially expressed genes from RNA-Seq and generated functional enrichment results after silencing of hnRNP Q and hnRNP R in neuroblastoma SH-SY5Y cell line. Interestingly, despite their high sequence similarity, these two proteins were found to affect different cellular pathways, especially with regards to neurodegeneration, such as PENK, NGR3, RAB26, JAG1, as well as inflammatory response, such as TNF, ICAM1, ICAM5, and TNFRSF9. In conclusion, human hnRNP Q and hnRNP R may be considered potentially important regulators of neuronal homeostasis and their disruption could impair distinct pathways in the central nervous system axis, thus confirming the importance of their conservation during evolution.
Highlights
Regulation of RNA metabolism is an important step in the maintenance of neuronal homeostasis
To better characterize the roles played by human Heteregeneous ribonucleoproteins (hnRNPs) Q and hnRNP R in the neuronal-like cell line SH-SY5Y, we first investigated their subcellular localization by carrying out immunofluorescence (IF) staining for the endogenous proteins
The elucidation of the molecular mechanisms underlying RNA regulation in both physiological and pathological processes is hampered by the great complexity of RNAbinding proteins (RBPs) networks, that can occur through the establishment of highly specific or loosely-specific interactions (Liachko et al, 2010; Cohen et al, 2015) and their post-translational modifications (Dassi, 2017)
Summary
Regulation of RNA metabolism is an important step in the maintenance of neuronal homeostasis. In 2004, a census of all the human proteins known to bind RNA or to be RNA-related identified ∼ 1,542 proteins (about 7.5% of all protein-coding genes) as potentially belonging to the RBP family (Gerstberger et al, 2014) This finding reflects a great importance for these hnRNPQ and hnRNPR Regulated DEG proteins during evolution, as a considerable number of ortholog of these human RBPs was found in the lower organisms, such as Archea and Bacteria (Anantharaman et al, 2002). In addition to the evolutionary conservation the importance of RBPs in the regulation of RNA metabolism is highlighted by the observation that highly complex tissues, such as brain, express a network of specific RBPs for regulating the RNA homeostasis (e.g., Hu/ELAV family) (De Conti et al, 2016)
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