scholarly journals Psip1/p52 regulates distal Hoxa genes through activation of lncRNA Hottip

2016 ◽  
Author(s):  
Madapura M Pradeepa ◽  
Gillian Taylor ◽  
Graeme R Grimes ◽  
Andrew J Wood ◽  
Wendy A Bickmore

AbstractLong noncoding RNAs (lncRNAs) have been implicated in various biological functions including regulation of gene expression, X-inactivation, imprinting, cell proliferation and differentiation. However, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that a transcriptional co activator – PC4 and SF2 interacting protein (Psip1)/p52, which is involved in linking transcription to RNA processing, regulates the expression of the lncRNA Hottip. Using complementary approaches – knockdown, Cas9 mediated lncRNA deletion, analysis of lncRNA binding by Chromatin isolation by RNA purification (ChIRP) - we demonstrate that Hottip binds to the 5’ Hoxa genes located in cis, which leads to their upregulation. Moreover, the synthetic activation of Hottip is sufficient to induce the expression ofpolycomb repressed Hox genes in mouse embryonic stem cells (mESCs).


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mengdie Cao ◽  
Xiangyuan Luo ◽  
Kongming Wu ◽  
Xingxing He

AbstractIn recent years, accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis. Lysosomal changes and dysfunction have been correlated with the development of numerous diseases. In this review, we interpreted the key biological functions of lysosomes in four areas: cellular metabolism, cell proliferation and differentiation, immunity, and cell death. More importantly, we actively sought to determine the characteristic changes and dysfunction of lysosomes in cells affected by these diseases, the causes of these changes and dysfunction, and their significance to the development and treatment of human disease. Furthermore, we outlined currently available targeting strategies: (1) targeting lysosomal acidification; (2) targeting lysosomal cathepsins; (3) targeting lysosomal membrane permeability and integrity; (4) targeting lysosomal calcium signaling; (5) targeting mTOR signaling; and (6) emerging potential targeting strategies. Moreover, we systematically summarized the corresponding drugs and their application in clinical trials. By integrating basic research with clinical findings, we discussed the current opportunities and challenges of targeting lysosomes in human disease.



2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Klaudia Kulczyńska ◽  
Miroslawa Siatecka

During recent years it has been discovered that long non-coding RNAs are important regulators in many biological processes. In this review, we summarize the role of lncRNA in erythropoiesis. LncRNA are crucial for regulation of gene expression during both proliferation and differentiation stages of red blood cell development. Many are regulated by erythroidspecific transcription factors and some are expressed in a developmental stage-specific manner. The majority of individually studied lncRNAs are involved in regulating the terminal maturation stages of red cell differentiation. Their regulatory function is accomplished by various mechanisms, including direct regulation in cis or trans by the lncRNA product or by the cis-localized presence of the lncRNA transcription itself. These add additional levels of regulation of gene expression during erythropoiesis.





2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Agnes Fütterer ◽  
Amaia Talavera-Gutiérrez ◽  
Tirso Pons ◽  
Jesús de Celis ◽  
Julio Gutiérrez ◽  
...  

AbstractEmbryonic stem cell (ESC) differentiation and somatic cell reprogramming are biological processes governed by antagonistic expression or repression of a largely common set of genes. Accurate regulation of gene expression is thus essential for both processes, and alterations in RNA processing are predicted to negatively affect both. We show that truncation of the DIDO gene alters RNA splicing and transcription termination in ESC and mouse embryo fibroblasts (MEF), which affects genes involved in both differentiation and reprogramming. We combined transcriptomic, protein interaction, and cellular studies to identify the underlying molecular mechanism. We found that DIDO3 interacts with the helicase DHX9, which is involved in R-loop processing and transcription termination, and that DIDO3-exon16 deletion increases nuclear R-loop content and causes DNA replication stress. Overall, these defects result in failure of ESC to differentiate and of MEF to be reprogrammed. MEF immortalization restored impaired reprogramming capacity. We conclude that DIDO3 has essential functions in ESC differentiation and somatic cell reprogramming by supporting accurate RNA metabolism, with its exon16-encoded domain playing the main role.





2008 ◽  
Vol 53 (No. 9) ◽  
pp. 457-468 ◽  
Author(s):  
L. Adlerova ◽  
A. Bartoskova ◽  
M. Faldyna

This review discusses the biological properties of the glycoprotein lactoferrin. Lactoferrin has been identified in secretions from exocrine glands and in specific granules of neutrophils. After degranulation, neutrophils become the main source of lactoferrin in blood plasma. Lactoferrin possesses various biological functions, including roles in iron metabolism, cell proliferation and differentiation, and antibacterial, antiviral, and antiparasitic activity. Many of these functions do not appear to be connected with its iron binding ability. Of late, lactoferrin concentrations have been measured mostly in humans but also in some other species. However, the relationship between its concentration and physiological or pathological effects on body functions is not yet well characterised.



2015 ◽  
Vol 89 (1-2) ◽  
pp. 42-50 ◽  
Author(s):  
Young Rae Ji ◽  
Hei Jung Kim ◽  
Si Jun Park ◽  
Ki Beom Bae ◽  
Seo Jin Park ◽  
...  


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