Functions of Heterogeneous Nuclear Ribonucleoproteins in Stem Cell Potency and Differentiation

Abstract

Stem cells possess huge importance in developmental biology, disease modelling, cell replacement therapy, and tissue engineering in regenerative medicine because they have the remarkable potential for self-renewal and to differentiate into almost all the cell types in the human body. Elucidation of molecular mechanisms regulating stem cell potency and differentiation is essential and critical for extensive application. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are modular proteins consisting of RNA-binding motifs and auxiliary domains characterized by extensive and divergent functions in nucleic acid metabolism. Multiple roles of hnRNPs in transcriptional and posttranscriptional regulation enable them to be effective gene expression regulators. More recent findings show that hnRNP proteins are crucial factors implicated in maintenance of stem cell self-renewal and pluripotency and cell differentiation. The hnRNPs interact with certain sequences in target gene promoter regions to initiate transcription. In addition, they recognize 3′UTR or 5′UTR of specific gene mRNA forming mRNP complex to regulate mRNA stability and translation. Both of these regulatory pathways lead to modulation of gene expression that is associated with stem cell proliferation, cell cycle control, pluripotency, and committed differentiation.

Novel Pathological Role of hnRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) in Vascular Smooth Muscle Cell Function and Neointima Hyperplasia

“…hnRNPs are modular proteins consisting of RNA-binding motifs and auxiliary domains characterized by extensive and divergent functions in nucleic acid metabolism. As such, a diverse function of the hnRNPs in gene regulation ranging from nascent transcript packaging to transcriptional regulation, alternative slicing, nucleocytoplasmic transport, and translational regulation of mRNA, has been increasingly reported in the literature25. Importantly, by using nuclear proteomics analyses we observed the two hnRNPs, hnRNPA113 and hnRNPA2B126, are closely regulated during VSMC differentiation from stem cells.…”

Identification and dynamic changes of RNAs isolated from RALY-containing ribonucleoprotein complexes

“…Studying the role of hnRNPs in cell cycle regulation and cell differentiation has recently opened a new exciting area of investigation (93). Our data together with data present in public data bank (e.g.…”

HnRNPA1 interacts with G-quadruplex in the TRA2B promoter and stimulates its transcription in human colon cancer cells

“…In the present study, we identified heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and hnRNPU as TRA2β4 -binding proteins using biotinylated RNA pull-down and RNA immunoprecipitation assays. The hnRNP family functions as major splicing factors as well as transcriptional regulators for various genes 17 . In fact, both hnRNPA1 and hnRNPU could upregulate the promoter activity of TRA2B .…”