Long Noncoding RNAs and RNA-Binding Proteins in Oxidative Stress, Cellular Senescence, and Age-Related Diseases

Table 2

A list of RBPs involved in DNA damage response, oxidative stress, cellular senescence, and age-related diseases.

RBPs	Functions	References
DNA damage response and oxidative stress
HuR	Protection roles in oxidative stress and DNA damage by regulating RNA metabolism (reviewed in 114, 115); Regulates HO1, WEE1, and NONO expression during stress response	[114–119]
hnRNP A0	Phosphorylation of hnRNP A0 by MK2 promotes GADD45α mRNA stabilization	[121]
hnRNP A18	Increases gene expression involved in stress-response	[122, 123]
hnRNP A1	Involved in alternative splicing of hdm2 and Apaf-1 translation	[124]
hnRNP C	Regulates BRCA gene expression and homologous recombination after ionizing irradiation	[125]
hnRNP H/F	Increased in DNA damage response and upregulates p53 expression	[126]
hnRNP I	Enhances translation of HIF-1α in hypoxia	[127]
FUS	Interacts with HDAC1 and regulates DNA damage response	[129]
TIA-1/TIAR	TIA-1/TIAR are involved in SG formation after stress response and decrease HIF-1α translation; TIA-1 oxidation by ROS suppresses SG formation and increases cell death; TIAR increases Apaf-1 translation after UVC-induced DNA damage	[130, 131, 133]
Wig1	Stabilizes p53 mRNA and enhancing p53-mediated stress response	[136]
Cellular senescence and aging
HuR	HuR loss is related to shorter life span and enhanced senescence-associated phenotypes (reviewed in 137); CARM1 downregulates HuR activity in replicative senescence	[137–139, 141]
AUF1	Involved in cellular senescence by regulating mRNA stability of p21 and p16, and AUF1 KO mice show enhanced cellular senescence and rapid premature aging	[142–144]
TIA-1/TIAR	Down-regulated in cellular senescence and TIA-1/TIAR depletion promotes cellular senescence of MEF cells	[140, 146]
CUGBP1	CUGBP1 phosphorylation promotes the binding to p21 mRNA in senescent cells; Regulates C/EBPβ and HDAC1 in the liver and fat of old mice	[148, 150, 151]
TTP	Upregulated in senescent cells and contributes to p53 accumulation by destabilizing E6-AP mRNA	[140, 154]
Wig1	Prevents premature senescence by destabilizing p21 mRNA	[155]
Neurodegenerative diseases
TDP-43	Functions as a translational repressor; Regulates axonal transport of RNA granules by interacting with hnRNP A2/B1; Mutants form of TDP-43 found in ALS patients are prone to aggregation	[160–162]
FUS	Interacts with DNA/RNA and regulates DNA/RNA metabolism; Mutation found in ALS patients are related to abnormal aggregation of FUS in cytoplasm and dysregulation of alternative splicing	[164]
HuD	Has pivotal roles in neurogenesis, axonal growth, and neuronal functions; Upregulated in the brain of AD patients and promotes Aβ accumulation	[166, 168]
FMRP	Mutations on FXP1 gene are linked to FXS, AD, and PD by dysregulation translation of target genes; Downregulated in the brain of sporadic AD patients and regulates APP translation	[170–172]
hnRNP A1	Loss of hnRNP A1 or mutations on D262 residue is found in the ALS patients; Downregulated in the brain of AD patients and affects to splicing of RAGE and APP mRNAs	[174, 175]
hnRNP A2/B1	Mutation on D290 residue dysregulates cellular stress response in ALS; Differentially expressed in the brain of AD and affects alternative splicing	[176, 177]
hnRNP C	Upregulated in the brain of AD patients; Stabilizes APP mRNA and enhances translation of APP	[171, 172]
Metabolic diseases
HuD	Downregulated in the pancreas of T2DM; Regulates insulin biosynthesis, autophagosome formation, lipid synthesis, and apoptosis in pancreatic β cells	[181–184]
CUGBP1	Upregulated in the diabetic hearts and the pancreas and regulates insulin secretion and insulin resistance; Obesity-related SNPs on CUGBP1 influence alternative splicing, translation, and turnover of target mRNAs	[185–187]
RBFOX2	Plays essential roles in alternative splicing; In diabetic hearts, majority of misspliced transcripts have RBFOX2-binding sites	[188, 189]
IGF2BP2/IMP	SNPs on IGF2BP2/IMP2 genes are associated to T2DM; IMP2 KO mice show better glucose tolerance, insulin sensitivity, and longer lifespan	[191–193]