Due to their capacity to mediate repetitive protein interactions, intrinsically disordered regions (IDRs) are crucial for the formation of various types of protein-RNA complexes. The functions of IDRs are strongly modulated by post-translational modifications (PTMs). Phosphorylation is the most common and well-studied modification of IDRs, which can alter homomeric or heteromeric interactions of proteins and impact their ability to phase separate. Moreover, phosphorylation can influence the RNA-binding properties of proteins, and recent studies demonstrated its selective impact on the global profiles of protein-RNA binding and regulation. These findings highlight the need for further integrative approaches to understand how signalling remodels protein-RNA networks in cells.

To survive and thrive in a dynamic environment, plants must continuously monitor their surroundings and adjust their development and physiology accordingly. Changes in gene expression underlie these developmental and physiological adjustments, and are traditionally attributed to widespread transcriptional reprogramming. Growing evidence, however, suggests that post-transcriptional mechanisms also play a vital role in tailoring gene expression to a plant\'s environment. Untranslated regions (UTRs) act as regulatory hubs for post-transcriptional control, harbouring cis-elements that affect an mRNA\'s processing, localization, translation, and stability, and thereby tune the abundance of the encoded protein. Here, we review recent advances made in understanding the critical function UTRs exert in the post-transcriptional control of gene expression in the context of a plant\'s abiotic environment. We summarize the molecular mechanisms at play, present examples of UTR-controlled signalling cascades, and discuss the potential that resides within UTRs to render plants more resilient to a changing climate.

Short for pyruvate kinase M2 subtype, PKM2 can be said of all-round player that is notoriously known for its metabolic involvement in glycolysis. Holding a dural role as a metabolic or non-metabolic (kinase) enzyme, PKM2 has drawn extensive attention over its biological roles implicated in tumor cells, including proliferation, migration, invasion, metabolism, and so on. wandering PKM2 can be transboundary both intracellularly and extracellularly. Specifically, PKM2 can be nuclear, cytoplasmic, mitochondrial, exosomal, or even circulate within the body. Importantly, PKM2 can function as an RNA-binding protein (RBP) to self-support its metabolic function. Despite extensive investigations or reviews available surrounding the biological roles of PKM2 from different angles in tumor cells, little has been described regarding some novel role of PKM2 that has been recently found, including, for example, acting as RNA-binding protein, protection of Golgi apparatus, and remodeling of microenvironment, and so forth. Given these findings, in this review, we summarize the recent advancements made in PKM2 research, mainly from non-metabolic respects. By the way, PKM1, another paralog of PKM2, seems to have been overlooked or under-investigated since its discovery. Some recent discoveries made about PKM1 are also preliminarily mentioned and discussed.

[This corrects the article DOI: 10.3389/fimmu.2023.1224516.].

RNA is integral to the regulatory circuits that control cell identity and behavior. Cis-regulatory elements in mRNAs interact with RNA-binding proteins (RBPs) that can alter RNA sequence, stability, and translation into protein. Similarly, long noncoding RNAs (lncRNAs) scaffold ribonucleoprotein complexes that mediate transcriptional and post-transcriptional regulation of gene expression. Indeed, cell programming is fundamental to multicellular life and, in this era of cellular therapies, it is of particular interest in T cells. Here, we review key concepts and recent advances in our understanding of the RNA circuits and RBPs that govern mammalian T cell differentiation and immune function.

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BP1, IGF2BP2, and IGF2BP3) are a family of RNA-binding proteins that play an essential role in the development and disease by regulating mRNA stability and translation of critical regulators of cell division and metabolism. Genetic and chemical inhibition of these proteins slows down cancer cell proliferation, decreases invasiveness, and prolongs life span in a variety of animal models. The role of RNA-binding proteins in the induction of tissues\' immunogenicity is increasingly recognized, but, the impact of the IGF2BPs family of proteins on the induction of innate and adaptive immune responses in cancer is not fully understood. Here we report that downregulation of IGF2BP1, 2, and 3 expression facilitates the expression of interferon beta-stimulated genes. IGF2BP1 has a greater effect on interferon beta and gamma signaling compared to IGF2BP2 and IGF2BP3 paralogs. We demonstrate that knockdown or knockout of IGF2BP1, 2, and 3 significantly potentiates inhibition of cell growth induced by IFNβ and IFNγ. Mouse melanoma cells with Igf2bp knockouts demonstrate increased expression of MHC I (H-2) and induce intracellular Ifn-γ expression in syngeneic T-lymphocytes in vitro. Increased immunogenicity, associated with Igf2bp1 inhibition, \"inflames\" mouse melanoma tumors microenvironment in SM1/C57BL/6 and SW1/C3H mouse models measured by a two-fold increase of NK cells and tumor-associated myeloid cells. Finally, we demonstrate that the efficiency of anti-PD1 immunotherapy in the mouse melanoma model is significantly more efficient in tumors that lack Igf2bp1 expression. Our retrospective data analysis of immunotherapies in human melanoma patients indicates that high levels of IGF2BP1 and IGF2BP3 are associated with resistance to immunotherapies and poor prognosis. In summary, our study provides evidence of the role of IGF2BP proteins in regulating tumor immunogenicity and establishes those RBPs as immunotherapeutic targets in cancer.

Neuroblastoma is the most common solid tumor in infants accounting for approximately 15% of all cancer-related deaths. Over 50% of high-risk neuroblastoma relapse, emphasizing the need of novel drug targets and therapeutic strategies. In neuroblastoma, chromosomal gains at chromosome 17q, including IGF2BP1, and MYCN amplification at chromosome 2p are associated with adverse outcome. Recent, pre-clinical evidence indicates the feasibility of direct and indirect targeting of IGF2BP1 and MYCN in cancer treatment.
Candidate oncogenes on 17q were identified by profiling the transcriptomic/genomic landscape of 100 human neuroblastoma samples and public gene essentiality data. Molecular mechanisms and gene expression profiles underlying the oncogenic and therapeutic target potential of the 17q oncogene IGF2BP1 and its cross-talk with MYCN were characterized and validated in human neuroblastoma cells, xenografts and PDX as well as novel IGF2BP1/MYCN transgene mouse models.
We reveal a novel, druggable feedforward loop of IGF2BP1 (17q) and MYCN (2p) in high-risk neuroblastoma. This promotes 2p/17q chromosomal gains and unleashes an oncogene storm resulting in fostered expression of 17q oncogenes like BIRC5 (survivin). Conditional, sympatho-adrenal transgene expression of IGF2BP1 induces neuroblastoma at a 100% incidence. IGF2BP1-driven malignancies are reminiscent to human high-risk neuroblastoma, including 2p/17q-syntenic chromosomal gains and upregulation of Mycn, Birc5, as well as key neuroblastoma circuit factors like Phox2b. Co-expression of IGF2BP1/MYCN reduces disease latency and survival probability by fostering oncogene expression. Combined inhibition of IGF2BP1 by BTYNB, MYCN by BRD inhibitors or BIRC5 by YM-155 is beneficial in vitro and, for BTYNB, also.
We reveal a novel, druggable neuroblastoma oncogene circuit settling on strong, transcriptional/post-transcriptional synergy of MYCN and IGF2BP1. MYCN/IGF2BP1 feedforward regulation promotes an oncogene storm harboring high therapeutic potential for combined, targeted inhibition of IGF2BP1, MYCN expression and MYCN/IGF2BP1-effectors like BIRC5.

As a master regulator in cells, RNA-binding protein (RBP) plays critical roles in organismal development, metabolism and various diseases. It regulates gene expression at various levels mostly by specific recognition of target RNA. The traditional CLIP-seq method to detect transcriptome-wide RNA targets of RBP is less efficient in yeast due to the low UV transmissivity of their cell walls. Here, we established an efficient HyperTRIBE (Targets of RNA-binding proteins Identified By Editing) in yeast, by fusing an RBP to the hyper-active catalytic domain of human RNA editing enzyme ADAR2 and expressing the fusion protein in yeast cells. The target transcripts of RBP were marked with new RNA editing events and identified by high-throughput sequencing. We successfully applied HyperTRIBE to identifying the RNA targets of two yeast RBPs, KHD1 and BFR1. The antibody-free HyperTRIBE has competitive advantages including a low background, high sensitivity and reproducibility, as well as a simple library preparation procedure, providing a reliable strategy for RBP target identification in Saccharomyces cerevisiae.

Acute myeloid leukaemia (AML) is one of the most lethal cancers of the haematopoietic system with a poorly understood aetiology. Recent studies have shown that aberrant alternative splicing (AS) and a (RBP) regulators are highly associated with the pathogenesis of AML. This study presents an overview of the abnormal AS and differential expression of RNA-binding proteins (RBPs) in AML and further highlights their close relation to the remodelling of the immune microenvironment in AML patients. An in-depth understanding of the regulatory mechanism underlying AML will contribute to the future development of strategies for the prevention, diagnosis and therapy of AML and thus improve the overall survival of patients with AML.

UNASSIGNED: Globally, liver cancer is one of the most common malignant tumors and is the third leading cause of cancer deaths. RNA-binding protein (RBP) is a general term for a class of proteins that bind to RNA to regulate metabolic processes. The expression of RNA-binding proteins is related to the prognosis of liver cancer patients.
UNASSIGNED: The RBP gene expression data of liver cancer were extracted from the TCGA database. First, the differentially expressed RBPs (DE RBPs) were selected through enrichment analysis and volcano mapping. Then, the prognosis-related RBP genes were selected through single-factor Cox regression analysis. The key prognosis-related RBPs were further screened by multifactor Cox regression analysis, and a formula for the patient\'s risk coefficient was obtained. Finally, based on the patient\'s risk score, a nomogram was established and verified.
UNASSIGNED: We extracted 374 cancer tissue samples and 50 normal tissue samples with the clinical information from each sample. Through enrichment analysis, we screened 208 upregulated RBPs and 122 downregulated RBPs. Prognosis-related high-risk genes were EEF1E1, NOP56, UPF3B, SF3B4, SMG5, CD3EAP, BRCA1, BARD1, XPO5, CSTF2, EZH2, EXO1, RRP12, PRIM1, LIN28B, NROB1 and TCOF1, and the low-risk genes were MRPL46, RCL1, MRPL54, CPEB3, IFIT5, PPARGC1A, EIF2AK4, SEPSECS, ACO1, SECISBP2 L and ZCCHC24. Further multivariate Cox regression analysis was performed on the prognosis-related RBPs, and the three key prognosis-related RBPs were screened out, which were BARD1, NR0B1 and EIF2AK4. A patient risk coefficient calculation formula was obtained: risk score = (1.207×BARD1 Exp) + (0.483×NR0B1 Exp) + (-0.720×EIF2AK4 Exp). Finally, a nomogram was established based on the risk score to predict the survival time of patients from 1 to 5 years.
UNASSIGNED: The nomogram has good predictive value for the survival time of liver cancer patients.