Functional diversity of the hnRNPs: past, present and perspectives

Han, Siew Ping; Tang, Yue; Smith, Ross

doi:10.1042/bj20100396

Cited by 454 publications

(442 citation statements)

References 207 publications

Supporting

Mentioning

432

Contrasting

Unclassified

Order By: Relevance

“…hnRNPs, which are among the most abundant nuclear proteins, stably associate with newly synthesized pre-mRNA, playing important roles in nuclear and cytoplasmic steps of mRNA metabolism (5). In particular, the mammalian hnRNP family consists of at least 24 structurally diverse polypeptides (6).…”

Section: Splicing and Alternative Splicingmentioning

confidence: 99%

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

et al. 2012

View full text Add to dashboard Cite

SummarySerine/arginine-rich (SR) proteins are among the most studied splicing regulators. They constitute a family of evolutionarily conserved proteins that, apart from their initially identified and deeply studied role in splicing regulation, have been implicated in genome stability, chromatin binding, transcription elongation, mRNA stability, mRNA export and mRNA translation. Remarkably, this list of SR protein activities seems far from complete, as unexpected functions keep being unraveled. An intriguing aspect that awaits further investigation is how the multiple tasks of SR proteins are concertedly regulated within mammalian cells. In this article, we first discuss recent findings regarding the regulation of SR protein expression, activity and accessibility. We dive into recent studies describing SR protein auto-regulatory feedback loops involving different molecular mechanisms such as unproductive splicing, microRNA-mediated regulation and translational repression. In addition, we take into account another step of regulation of SR proteins, presenting new findings about a variety of post-translational modifications by proteomics approaches and how some of these modifications can regulate SR protein sub-cellular localization or stability. Towards the end, we focus in two recently revealed functions of SR proteins beyond mRNA biogenesis and metabolism, the regulation of micro-RNA processing and the regulation of small ubiquitin-like modifier (SUMO) conjugation.

show abstract

Section: Splicing and Alternative Splicingmentioning

confidence: 99%

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

et al. 2012

View full text Add to dashboard Cite

show abstract

“…3), none of the p values derived from methyl-arginine quantitative data for site AML and BC samples passed Benjamini-Hochberg critical value analysis (Supplemental Table S3), which indicates similar levels of arginine mono-methylation levels between AML and BC. There were, however, significant differences in site abundance between NSCLC serum samples compared with AML or BC, including heterogeneous nuclear ribonucleoproteins, well-studied RNA processing proteins involved in posttranscriptional modification of pre-mRNA (42). Methylation of hnRNP family members containing the RGG motif promotes import into the nucleus (43).…”

Section: Fig 2 Functional Classification Of Functions Of Proteins Imentioning

confidence: 99%

Quantitative Profiling of Post-translational Modifications by Immunoaffinity Enrichment and LC-MS/MS in Cancer Serum without Immunodepletion

Ren

Jia

et al. 2016

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Biomarker identification is a key step for illustration of disease mechanisms, drug development, and diagnostics. Diagnostics research has focused on identifying biomarkers from viable biofluids, including serum/plasma, saliva, cerebrospinal fluid, and urine. Due to ease of collection and richness in proteins and metabolites, serum/plasma has been the preferred choice for diagnostic studies (1-3). Advancement of mass-spectrometry-based proteomic technologies has allowed identification and quantification of thousands of proteins in serum/plasma samples. Typically, these methods combine isotopic labeling, offline fractionation, and LC-MS/MS analysis. Facilitated by high-throughput proteomics analysis, researchers have collected vast amounts of comparative information about protein abundance in serum/plasma of patients of various types of diseases that accelerated the identification of potential biomarkers (4).To date, the majority of serum/plasma proteomic work has been conducted to analyze total protein level abundance, with only a few studies to analyze posttranslational modifications (PTMs) 1 , usually glycosylation (5, 6). As one of the most important mechanisms for regulating protein function, PTMs, including phosphorylation, acetylation, ubiquitination, and methylation, have been identified and validated as critical for signaling transduction, protein degradation, and transcriptional regulation (7,8). Currently, there exists very limited data about PTMs in serum/plasma beyond glycosylation. The abundant serum protein albumin has long been known to be acetylated by aspirin, and this reaction can occur in vitro without the presence of any acetyltransferase (9). Fibrinogen, another abundant serum protein, is also acetylated by aspirin both in vivo and in vitro (10, 11). These previous findings and the known importance of PTMs in cellular signaling provided the impetus for a large-scale survey of PTMs other than glycosylation by immunoaffinity enrichment of PTM-containing peptides.One challenge for proteomic analysis of serum/plasma is the broad dynamic range of the serum/plasma proteome (12), including a high percentage of the total protein content of serum/plasma represented by only 12 proteins. This limitation can be partially overcome by immunodepletion of abundant proteins prior to enzymatic digestion (4, 13), however, generation of the large quantities of materials necessary for PTM enrichment with an immunodepletion workflow could be cost prohibitive. It was therefore of interest to develop a PTM

show abstract

“…2 Domain composition among hnRNP members is highly diverse. Some show classical RRM or KH domains, 3 while hnRNP H1, hnRNP H2 and hnRNP F exhibit the so called quasi-RRMs (or qRRM) domains. 3,5 In this study, we deeply characterize hnRNP H1.…”

Section: Introductionmentioning

confidence: 99%

“…Some show classical RRM or KH domains, 3 while hnRNP H1, hnRNP H2 and hnRNP F exhibit the so called quasi-RRMs (or qRRM) domains. 3,5 In this study, we deeply characterize hnRNP H1. This protein tends to form a heterodimer with hnRNP F and shows preference for G-rich tracts of RNA.…”

Section: Introductionmentioning

confidence: 99%

High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

et al. 2016

View full text Add to dashboard Cite

ABSTRACThnRNPs are polyvalent RNA binding proteins that have been implicated in a range of regulatory roles including splicing, mRNA decay, translation, and miRNA metabolism. A variety of genome wide studies have taken advantage of methods like CLIP and RIP to identify the targets and binding sites of RNA binding proteins. However, due to the complex nature of RNA-binding proteins, these studies are incomplete without assays that characterize the impact of RBP binding on mRNA target expression. Here we used a suite of high-throughput approaches (RIP-Seq, iCLIP, RNA-Seq and shotgun proteomics) to provide a comprehensive view of hnRNP H1s ensemble of targets and its role in splicing, mRNA decay, and translation. The combination of RIP-Seq and iCLIP allowed us to identify a set of 1,086 high confidence target transcripts. Binding site motif analysis of these targets suggests the TGGG tetramer as a prevalent component of hnRNP H1 binding motif, with particular enrichment around intronic hnRNP H1 sites. Our analysis of the target transcripts and binding sites indicates that hnRNP H1s involvement in splicing is 2-fold: it directly affects a substantial number of splicing events, but also regulates the expression of major components of the splicing machinery and other RBPs with known roles in splicing regulation. The identified mRNA targets displayed function enrichment in MAPK signaling and ubiquitin mediated proteolysis, which might be main routes by which hnRNP H1 promotes tumorigenesis.

show abstract

Functional diversity of the hnRNPs: past, present and perspectives

Cited by 454 publications

References 207 publications

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

Regulating the regulators: Serine/arginine‐rich proteins under scrutiny

Quantitative Profiling of Post-translational Modifications by Immunoaffinity Enrichment and LC-MS/MS in Cancer Serum without Immunodepletion

High-throughput analyses of hnRNP H1 dissects its multi-functional aspect

Contact Info

Product

Resources

About