scholarly journals Regulation of Paneth Cell Function by RNA-Binding Proteins and Noncoding RNAs

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2107
Author(s):  
Hee K. Chung ◽  
Lan Xiao ◽  
Krishna C. Jaladanki ◽  
Jian-Ying Wang

Paneth cells are specialized intestinal epithelial cells that are located at the base of small intestinal crypts and play a vital role in preserving the gut epithelium homeostasis. Paneth cells act as a safeguard from bacterial translocation across the epithelium and constitute the niche for intestinal stem cells in the small intestine by providing multiple niche signals. Recently, Paneth cells have become the focal point of investigations defining the mechanisms underlying the epithelium-microbiome interactions and pathogenesis of chronic gut mucosal inflammation and bacterial infection. Function of Paneth cells is tightly regulated by numerous factors at different levels, while Paneth cell defects have been widely documented in various gut mucosal diseases in humans. The post-transcription events, specific change in mRNA stability and translation by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) are implicated in many aspects of gut mucosal physiology by modulating Paneth cell function. Deregulation of RBPs and ncRNAs and subsequent Paneth cell defects are identified as crucial elements of gut mucosal pathologies. Here, we overview the posttranscriptional regulation of Paneth cells by RBPs and ncRNAs, with a particular focus on the increasing evidence of RBP HuR and long ncRNA H19 in this process. We also discuss the involvement of Paneth cell dysfunction in altered susceptibility of the intestinal epithelium to chronic inflammation and bacterial infection following disrupted expression of HuR and H19.

2019 ◽  
Vol 14 (7) ◽  
pp. 621-627 ◽  
Author(s):  
Youhuang Bai ◽  
Xiaozhuan Dai ◽  
Tiantian Ye ◽  
Peijing Zhang ◽  
Xu Yan ◽  
...  

Background: Long noncoding RNAs (lncRNAs) are endogenous noncoding RNAs, arbitrarily longer than 200 nucleotides, that play critical roles in diverse biological processes. LncRNAs exist in different genomes ranging from animals to plants. Objective: PlncRNADB is a searchable database of lncRNA sequences and annotation in plants. Methods: We built a pipeline for lncRNA prediction in plants, providing a convenient utility for users to quickly distinguish potential noncoding RNAs from protein-coding transcripts. Results: More than five thousand lncRNAs are collected from four plant species (Arabidopsis thaliana, Arabidopsis lyrata, Populus trichocarpa and Zea mays) in PlncRNADB. Moreover, our database provides the relationship between lncRNAs and various RNA-binding proteins (RBPs), which can be displayed through a user-friendly web interface. Conclusion: PlncRNADB can serve as a reference database to investigate the lncRNAs and their interaction with RNA-binding proteins in plants. The PlncRNADB is freely available at http://bis.zju.edu.cn/PlncRNADB/.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Haiyan Shen ◽  
Guomin Luo ◽  
Qingjuan Chen

AbstractApproximately 338,000 patients are diagnosed with kidney cancer worldwide each year, and renal cell carcinoma (RCC), which is derived from renal epithelium, accounts for more than ninety percent of the malignancy. Next generation RNA sequencing has enabled the identification of novel long noncoding RNAs (lncRNAs) in the past 10 years. Recent studies have provided extensive evidence that lncRNAs bind to chromatin modification proteins, transcription factors, RNA-binding proteins and microRNAs, and thereby modulate gene expression through regulating chromatin status, gene transcription, pre-mRNA splicing, mRNA decay and stability, protein translation and stability. In vitro and in vivo studies have demonstrated that over-expression of oncogenic lncRNAs and silencing of tumor suppressive lncRNAs are a common feature of human RCC, and that aberrant lncRNA expression is a marker for poor patient prognosis, and is essential for the initiation and progression of RCC. Because lncRNAs, compared with mRNAs, are expressed in a tissue-specific manner, aberrantly expressed lncRNAs can be better targeted for the treatment of RCC through screening small molecule compounds which block the interaction between lncRNAs and their binding proteins or microRNAs.


Author(s):  
J. J. David Ho ◽  
Jeffrey H. S. Man ◽  
Jonathan H. Schatz ◽  
Philip A. Marsden

2003 ◽  
Vol 23 (19) ◽  
pp. 7055-7067 ◽  
Author(s):  
Shelly A. Waggoner ◽  
Stephen A. Liebhaber

ABSTRACT Posttranscriptional controls in higher eukaryotes are central to cell differentiation and developmental programs. These controls reflect sequence-specific interactions of mRNAs with one or more RNA binding proteins. The α-globin poly(C) binding proteins (αCPs) comprise a highly abundant subset of K homology (KH) domain RNA binding proteins and have a characteristic preference for binding single-stranded C-rich motifs. αCPs have been implicated in translation control and stabilization of multiple cellular and viral mRNAs. To explore the full contribution of αCPs to cell function, we have identified a set of mRNAs that associate in vivo with the major αCP2 isoforms. One hundred sixty mRNA species were consistently identified in three independent analyses of αCP2-RNP complexes immunopurified from a human hematopoietic cell line (K562). These mRNAs could be grouped into subsets encoding cytoskeletal components, transcription factors, proto-oncogenes, and cell signaling factors. Two mRNAs were linked to ceroid lipofuscinosis, indicating a potential role for αCP2 in this infantile neurodegenerative disease. Surprisingly, αCP2 mRNA itself was represented in αCP2-RNP complexes, suggesting autoregulatory control of αCP2 expression. In vitro analyses of representative target mRNAs confirmed direct binding of αCP2 within their 3′ untranslated regions. These data expand the list of mRNAs that associate with αCP2 in vivo and establish a foundation for modeling its role in coordinating pathways of posttranscriptional gene regulation.


2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Masahiro Onoguchi ◽  
Chao Zeng ◽  
Ayako Matsumaru ◽  
Michiaki Hamada

Abstract Recent reports have revealed that repeat-derived sequences embedded in introns or long noncoding RNAs (lncRNAs) are targets of RNA-binding proteins (RBPs) and contribute to biological processes such as RNA splicing or transcriptional regulation. These findings suggest that repeat-derived RNAs are important as scaffolds of RBPs and functional elements. However, the overall functional sequences of the repeat-derived RNAs are not fully understood. Here, we show the putative functional repeat-derived RNAs by analyzing the binding patterns of RBPs based on ENCODE eCLIP data. We mapped all eCLIP reads to repeat sequences and observed that 10.75 % and 7.04 % of reads on average were enriched (at least 2-fold over control) in the repeats in K562 and HepG2 cells, respectively. Using these data, we predicted functional RNA elements on the sense and antisense strands of long interspersed element 1 (LINE1) sequences. Furthermore, we found several new sets of RBPs on fragments derived from other transposable element (TE) families. Some of these fragments show specific and stable secondary structures and are found to be inserted into the introns of genes or lncRNAs. These results suggest that the repeat-derived RNA sequences are strong candidates for the functional RNA elements of endogenous noncoding RNAs.


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