scholarly journals Long noncoding RNA regulation of spermatogenesis via the spectrin cytoskeleton inDrosophila

Author(s):  
Mark J Bouska ◽  
Hua Bai

AbstractThe spectrin cytoskeleton has been shown to be critical in diverse processes such as axon development and degeneration, myoblast fusion, and spermatogenesis. Spectrin can be modulated in a tissue specific manner through junctional protein complexes, however, it has not been shown that long noncoding RNAs (lncRNAs) interact with and modulate spectrin. Here, we provide evidence of a lncRNA CR45362 that interacts with α-Spectrin, is required for spermatid nuclear bundling during Drosophila spermatogenesis. We observed that CR45362 showed high expression in the cyst cells at the basal testis, and CRISPR-mediated knockout of CR45362 led to sterile male, unbundled spermatid nuclei, and disrupted actin cones. Through chromatin isolation by RNA precipitation—mass spectrometry (ChIRP-MS), we identified actin-spectrin cytoskeletal components physically interact with the lncRNA CR45362. Genetic screening on identified cytoskeletal factors revealed that cyst cell-specific knockdown of α-Spectrin phenocopied CR45362 mutants and resulted in spermatid nuclear bundle defects. Consistently, CR45362 knockout disrupted the co-localization of α-Spectrin and spermatid nuclear bundles in the head cyst cells at the basal testis. Thus, we uncovered a novel lncRNA CR45362 that interacts with α-Spectrin to stabilize spermatid nuclear bundles during spermatid maturation.

2020 ◽  
Author(s):  
Mark J Bouska ◽  
Hua Bai

ABSTRACTThe spectrin cytoskeleton has been shown to be critical in diverse processes such as axon development and degeneration, myoblast fusion, and spermatogenesis. Spectrin can be modulated in a tissue specific manner through junctional protein complexes, however, it has not been shown that lncRNAs interact with and regulate spectrin. Here we provide evidence of a lncRNA that interacts with α and β Spectrin to regulate spermatogenesis and endosomal related activity in fat bodies of Drosophila. Protein-RNA and Protein-Protein biochemical analysis indicated the interaction between α and β Spectrin is modulated by the lncRNA CR45362. Immunocytochemistry revealed CR45362 is highly expressed in the basal testis while α and β Spectrin are clearly disrupted in this same region of CR45362 mutants. We genetically demonstrate α-Spectrin and CR45362 deficiencies cause spermatid nuclear bundling defects with congruous changes of spectrin distribution and reduced Lysotracker staining in the fat body. Our data suggests lncRNA regulation of spectrin could provide cells with a repertoire of modulatory molecules to manipulate cell-type specific cytoskeletal and endosomal requirements.


2018 ◽  
Vol 62 (11-12) ◽  
pp. 693-704 ◽  
Author(s):  
Ana Casaca ◽  
Gabriel M. Hauswirth ◽  
Heidi Bildsoe ◽  
Moisés Mallo ◽  
Edwina McGlinn

Precise regulation of Hox gene activity is essential to achieve proper control of animal embryonic development and to avoid generation of a variety of malignancies. This is a multilayered process, including complex polycistronic transcription, RNA processing, microRNA repression, long noncoding RNA regulation and sequence-specific translational control, acting together to achieve robust quantitative and qualitative Hox protein output. For many such mechanisms, the Hox cluster gene network has turned out to serve as a paradigmatic model for their study. In this review, we discuss current knowledge of how the different layers of post-transcriptional regulation and the production of a variety of noncoding RNA species control Hox output, and how this shapes formation of developmental systems that are reproducibly patterned by complex Hox networks.


Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 929 ◽  
Author(s):  
Raheleh Amirkhah ◽  
Hojjat Naderi-Meshkin ◽  
Jaynish Shah ◽  
Philip Dunne ◽  
Ulf Schmitz

Colorectal cancer (CRC) results from a transformation of colonic epithelial cells into adenocarcinoma cells due to genetic and epigenetic instabilities, alongside remodelling of the surrounding stromal tumour microenvironment. Epithelial-specific epigenetic variations escorting this process include chromatin remodelling, histone modifications and aberrant DNA methylation, which influence gene expression, alternative splicing and function of non-coding RNA. In this review, we first highlight epigenetic modulators, modifiers and mediators in CRC, then we elaborate on causes and consequences of epigenetic alterations in CRC pathogenesis alongside an appraisal of the complex feedback mechanisms realized through alternative splicing and non-coding RNA regulation. An emphasis in our review is put on how this intricate network of epigenetic and post-transcriptional gene regulation evolves during the initiation, progression and metastasis formation in CRC.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jinlong Wei ◽  
Bin Wang ◽  
Huanhuan Wang ◽  
Lingbin Meng ◽  
Qin Zhao ◽  
...  

Radiotherapy (RT) is currently one of the leading treatments for various cancers; however, it may cause damage to healthy tissue, with both short-term and long-term side effects. Severe radiation-induced normal tissue damage (RINTD) frequently has a significant influence on the progress of RT and the survival and prognosis of patients. The redox system has been shown to play an important role in the early and late effects of RINTD. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are the main sources of RINTD. The free radicals produced by irradiation can upregulate several enzymes including nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), lipoxygenases (LOXs), nitric oxide synthase (NOS), and cyclooxygenases (COXs). These enzymes are expressed in distinct ways in various cells, tissues, and organs and participate in the RINTD process through different regulatory mechanisms. In recent years, several studies have demonstrated that epigenetic modulators play an important role in the RINTD process. Epigenetic modifications primarily contain noncoding RNA regulation, histone modifications, and DNA methylation. In this article, we will review the role of oxidative stress and epigenetic mechanisms in radiation damage, and explore possible prophylactic and therapeutic strategies for RINTD.


2018 ◽  
Author(s):  
Sheng Xu ◽  
LuYu Zhou ◽  
Murugavel Ponnusamy ◽  
LiXia Zhang ◽  
Kun Wang

Circular RNA (CircRNA) is an endogenous noncoding RNA with covalently closed cyclic structure. It is divided into exonic circRNA, intronic circRNA and exon-intron circRNA, based on their components. CircRNAs are well conserved in sequence and abundantly expressed in a tissue specific manner. They have a high stability due to resistance to exonuclease. Depends on their sequence, they perform many biological function including microRNA sponging activity, modulation of alternative splicing or transcription, interaction with RNA binding proteins, rolling translation and derivative of pseudogenes. They are involved in the development of a variety pathological condition including cardiovascular disease, diabetes, neurological diseases and cancer. Emerging evidences show that circRNA are likely to be potential targets for new clinical diagnostic markers or treatment of many diseases. In this review, we have described the potential relationship between circRNA and disease progression, methods and databases of cyclic RNA.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Seahyoung Lee ◽  
Hyang-Hee Seo ◽  
Chang Youn Lee ◽  
Jiyun Lee ◽  
Sunhye Shin ◽  
...  

Because of their capability of differentiation into lineage-specific cells, stem cells are an attractive therapeutic modality in regenerative medicine. To develop an effective stem cell-based therapeutic strategy with predictable results, deeper understanding of the underlying molecular mechanisms of stem cell differentiation and/or pluripotency maintenance is required. Thus, reviewing the key factors involved in the transcriptional and epigenetic regulation of stem cell differentiation and maintenance is important. Accumulating data indicate that long noncoding RNAs (lncRNAs) mediate numerous biological processes, including stem cell differentiation and maintenance. Here, we review recent findings on the human lncRNA regulation of stem cell potency and differentiation. Although the clinical implication of these lncRNAs is only beginning to be elucidated, it is anticipated that lncRNAs will become important therapeutic targets in the near future.


2016 ◽  
Vol 29 (3) ◽  
pp. 155-155
Author(s):  
John P. Carr ◽  
Steven A. Whitham

Investigations in recent years have uncovered important roles for RNA molecules that do not encode proteins (‘noncoding RNAs’) but which, nevertheless, exert powerful effects on gene expression at both transcriptional and posttranscriptional levels. Our late colleague Biao Ding, who died unexpectedly on June 25, 2015, proposed a Focus Issue on the roles in plant-microbe interactions of noncoding RNAs, whether of plant or microbial origin and including small interfering (si)RNAs, microRNAs, phased siRNAs, and long noncoding RNAs, as well as viroids and satellite RNAs. The Editorial Board of MPMI has decided to dedicate this Focus Issue to the memory of Professor Biao Ding, a valued and deeply missed colleague and friend.


2020 ◽  
Vol 48 (16) ◽  
pp. 9301-9319 ◽  
Author(s):  
Jens Hör ◽  
Silvia Di Giorgio ◽  
Milan Gerovac ◽  
Elisa Venturini ◽  
Konrad U Förstner ◽  
...  

Abstract Stable protein complexes, including those formed with RNA, are major building blocks of every living cell. Escherichia coli has been the leading bacterial organism with respect to global protein-protein networks. Yet, there has been no global census of RNA/protein complexes in this model species of microbiology. Here, we performed Grad-seq to establish an RNA/protein complexome, reconstructing sedimentation profiles in a glycerol gradient for ∼85% of all E. coli transcripts and ∼49% of the proteins. These include the majority of small noncoding RNAs (sRNAs) detectable in this bacterium as well as the general sRNA-binding proteins, CsrA, Hfq and ProQ. In presenting use cases for utilization of these RNA and protein maps, we show that a stable association of RyeG with 30S ribosomes gives this seemingly noncoding RNA of prophage origin away as an mRNA of a toxic small protein. Similarly, we show that the broadly conserved uncharacterized protein YggL is a 50S subunit factor in assembled 70S ribosomes. Overall, this study crucially extends our knowledge about the cellular interactome of the primary model bacterium E. coli through providing global RNA/protein complexome information and should facilitate functional discovery in this and related species.


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