Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RNA-binding protein hnRNP Q has been implicated in neuronal mRNA metabolism. Here, we show that knockdown of hnRNP Q increased neurite complexity in cultured rat cortical neurons and induced filopodium formation in mouse neuroblastoma cells. Reexpression of hnRNP Q1 in hnRNP Q-depleted cells abrogated the morphological changes of neurites, indicating a specific role for hnRNP Q1 in neuronal morphogenesis. A search for mRNA targets of hnRNP Q1 identified functionally coherent sets of mRNAs encoding factors involved in cellular signaling or cytoskeletal regulation and determined its preferred binding sequences. We demonstrated that hnRNP Q1 bound to a set of identified mRNAs encoding the components of the actin nucleation-promoting Cdc42/N-WASP/Arp2/3 complex and was in part colocalized with Cdc42 mRNA in granules. Using subcellular fractionation and immunofluorescence, we showed that knockdown of hnRNP Q reduced the level of some of those mRNAs in neurites and redistributed their encoded proteins from neurite tips to soma to different extents. Overexpression of dominant negative mutants of Cdc42 or N-WASP compromised hnRNP Q depletion-induced neurite complexity. Together, our results suggest that hnRNP Q1 may participate in localization of mRNAs encoding Cdc42 signaling factors in neurites, and thereby may regulate actin dynamics and control neuronal morphogenesis.
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PMID:hnRNP Q regulates Cdc42-mediated neuronal morphogenesis. 2249 61

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.
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PMID:Systematic Analysis of Gene Expression Profiles Controlled by hnRNP Q and hnRNP R, Two Closely Related Human RNA Binding Proteins Implicated in mRNA Processing Mechanisms. 3021 3

Misfolded proteins with abnormal polyglutamine (polyQ) expansion cause neurodegenerative disorders, including Huntington's disease. Recently, it was found that polyQ aggregates accumulate as a result of vaccinia-related kinase 2 (VRK2)-mediated degradation of TCP-1 ring complex (TRiC)/chaperonin-containing TCP-1 (CCT), which has an essential role in the prevention of polyQ protein aggregation and cytotoxicity. The levels of VRK2 are known to be much higher in actively proliferating cells but are maintained at a low level in the brain via an unknown mechanism. Here, we found that basal levels of neuronal cell-specific VRK2 mRNA are maintained by post-transcriptional, rather than transcriptional, regulation. Moreover, heterogeneous nuclear ribonucleoprotein Q (HNRNP Q) specifically binds to the 3'untranslated region of VRK2 mRNA in neuronal cells to reduce the mRNA stability. As a result, we found a dramatic decrease in CCT4 protein levels in response to a reduction in HNRNP Q levels, which was followed by an increase in polyQ aggregation in human neuroblastoma cells and mouse cortical neurons. Taken together, these results provide new insights into how neuronal HNRNP Q decreases VRK2 mRNA stability and contributes to the prevention of Huntington's disease, while also identifying new prognostic markers of HD.
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PMID:HNRNP Q suppresses polyglutamine huntingtin aggregation by post-transcriptional regulation of vaccinia-related kinase 2. 3048 34