bsAS, an antisense long non-coding RNA, essential for correct wing development through regulation of blistered/DSRF isoform usage

Natural Antisense Transcripts (NATs) are long non-coding RNAs (lncRNAs) that overlap coding genes in the opposite strand. NATs roles have been related to gene regulation through different mechanisms, including post-transcriptional RNA processing. With the aim to identify NATs with potential regulatory function during fly development, we generated RNA-Seq data in Drosophila developing tissues and found bsAS, one of the most highly expressed lncRNAs in the fly wing. bsAS is antisense to bs/DSRF, a gene involved in wing development and neural processes. bsAS plays a crucial role in the tissue specific regulation of the expression of the bs/DSRF isoforms. This regulation is essential for the correct determination of cell fate during Drosophila development, as bsAS knockouts show highly aberrant phenotypes. Regulation of bs isoform usage by bsAS is mediated by specific physical interactions between the promoters of these two genes, which suggests a regulatory mechanism involving the collision of RNA polymerases transcribing in opposite directions. Evolutionary analysis suggests that bsAS NAT emerged simultaneously to the long-short isoform structure of bs, preceding the emergence of wings in insects.

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bsAS, an antisense long non-coding RNA, controls cell fate through regulation of blistered/DSRF isoform expression

10.1101/846451 ◽

2019 ◽

Author(s):

Sílvia Pérez-Lluch ◽

Alessandra Breschi ◽

Cecilia C. Klein ◽

Marina Ruiz-Romero ◽

Amaya Abad ◽

...

Keyword(s):

Cell Fate ◽

Protein Isoforms ◽

Regulatory Function ◽

Physical Interaction ◽

Evolutionary Analysis ◽

Rna Seq ◽

Non Coding Rna ◽

Neural Processes ◽

Correct Determination ◽

Opposite Strand

SummaryNatural Antisense Transcripts (NATs) are long non-coding RNAs (lncRNAs) that overlap coding genes in the opposite strand. NATs roles have been related to gene regulation through different mechanisms, including post-transcriptional RNA processing. With the aim to identify NATs with potential regulatory function during fly development, we generated RNA-Seq data in eye-antenna, leg, and wing at third instar larvae. Among the candidate NATs, we found bsAS, antisense to bs/DSRF, a gene involved in wing development and neural processes. Through the analysis of the RNA-Seq data, we found that these two different functions are carried out by the two different protein isoforms encoded in the bs gene. We also found that the usage of these isoforms is regulated by bsAS. This regulation is essential for the correct determination of cell fate during Drosophila development, as bsAS knockouts show highly aberrant phenotypes. bs regulation by bsAS is mediated by the specific physical interaction of the bsAS promoter with the promoters of bs, and it likely involves a mechanism, where expression of bsAS leads to the collision of RNA polymerases acting in opposite directions, preventing the elongation of the longer isoforms of bs, the ones carrying the neural related functions. Evolutionary analysis suggests that the bsAS NAT emerged simultaneously to the long-short isoform structure of bs, preceding the emergence of wings in insects, and maybe related to regulation of neural differentiation.

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MiR-7 in Cancer Development

Biomedicines ◽

10.3390/biomedicines9030325 ◽

2021 ◽

Vol 9 (3) ◽

pp. 325

Author(s):

Petra Korać ◽

Mariastefania Antica ◽

Maja Matulić

Keyword(s):

Cell Fate ◽

Dominant Role ◽

Tumor Development ◽

Mrna Translation ◽

Cell Types ◽

Fine Tuning ◽

Non Coding Rna ◽

Tumor Types ◽

Different Cell Types ◽

The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

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RNA sequencing reveals a key role for the long non-coding RNA MIAT in regulating neuroblastoma and glioblastoma cell fate

International Journal of Biological Macromolecules ◽

10.1016/j.ijbiomac.2019.03.005 ◽

2019 ◽

Vol 130 ◽

pp. 878-891 ◽

Cited By ~ 8

Author(s):

Aikaterini Bountali ◽

Daniel P. Tonge ◽

Mirna Mourtada-Maarabouni

Keyword(s):

Rna Sequencing ◽

Cell Fate ◽

Glioblastoma Cell ◽

Non Coding Rna ◽

Long Non Coding Rna

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The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes

Development ◽

10.1242/dev.113.1.245 ◽

1991 ◽

Vol 113 (1) ◽

pp. 245-255 ◽

Cited By ~ 32

Author(s):

M. Van Doren ◽

H.M. Ellis ◽

J.W. Posakony

Keyword(s):

Dna Binding ◽

Cell Fate ◽

Protein Complexes ◽

Competitive Inhibitor ◽

Binding Activity ◽

Regulatory Function ◽

Biochemical Basis ◽

Dna Binding Activity

In Drosophila, a group of regulatory proteins of the helix-loop-helix (HLH) class play an essential role in conferring upon cells in the developing adult epidermis the competence to give rise to sensory organs. Proteins encoded by the daughterless (da) gene and three genes of the achaete-scute complex (AS-C) act positively in the determination of the sensory organ precursor cell fate, while the extramacrochaetae (emc) and hairy (h) gene products act as negative regulators. In the region upstream of the achaete gene of the AS-C, we have identified three ‘E box’ consensus sequences that are bound specifically in vitro by hetero-oligomeric complexes consisting of the da protein and an AS-C protein. We have used this DNA-binding activity to investigate the biochemical basis of the negative regulatory function of emc. Under the conditions of our experiments, the emc protein, but not the h protein, is able to antagonize specifically the in vitro DNA-binding activity of da/AS-C and putative da/da protein complexes. We interpret these results as follows: the heterodimerization capacity of the emc protein (conferred by its HLH domain) allows it to act in vivo as a competitive inhibitor of the formation of functional DNA-binding protein complexes by the da and AS-C proteins, thereby reducing the effective level of their transcriptional regulatory activity within the cell.

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LINC00839 Knockdown Restrains The Metastatic Behaviors of Nasopharyngeal Carcinoma By Sponging miR-454-3p

10.21203/rs.3.rs-606939/v1 ◽

2021 ◽

Author(s):

Feng Ying Zhang ◽

Xia Li ◽

Ting Ting Huang ◽

Mei Ling Xiang ◽

Lin Lin Sun ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Underlying Mechanism ◽

Luciferase Reporter ◽

Regulatory Function ◽

Migration And Invasion ◽

Luciferase Reporter Gene ◽

Non Coding Rna ◽

Invasive Capacity

Abstract Background Long intergenic non-coding RNA 00839 (LINC00839) has been verified as a cancer-promoting gene in malignancies. However, the significance of LINC00839 in nasopharyngeal carcinoma (NPC) has yet to be elaborated, as well as its underlying mechanism.Methods LINC00839 and miR-454-3p relative expression levels in NPC cells were examined by qRT-PCR. The growth of cells was examined by CCK-8 and colony formation assays. Cell migration and invasion were examined by wound healing and Transwell experiment, respectively. The binding sequence of LINC00839 and miR-454-3p was confirmed by the luciferase reporter gene experiment. The regulatory function of LINC00839 and miR-454-3p on c-Met was investigated by western blot.Results Here, we revealed that LINC00839 was elevated in NPC. Both LINC00839 knockdown and upregulation of miR-454-3p suppressed NPC cells proliferation, invasive capacity and EMT in vitro. Besides, LINC00839 was validated as a miR-454-3p “sponge”, and upregulation of LINC00839 could reverse miR-454-3p-mediated functions in NPC C666-1 and SUNE-1 cells. Furthermore, c-Met was determined to be targeted by miR-454-3p. Notably, c-Met was downregulated by LINC00839 knockdown through sponging miR-454-3p. In vivo, LINC00839 knockdown resulted in a slower tumor growth.Conclusions Altogether, knockdown of LINC00839 inhibits the aggressive properties of NPC cells via sponging miR-454-3p and regulating c-Met.

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Gene Expression Profile of RNA N1-methyladenosine methyltransferases

E3S Web of Conferences ◽

10.1051/e3sconf/202021803052 ◽

2020 ◽

Vol 218 ◽

pp. 03052

Author(s):

Mingzhu Rao

Keyword(s):

Gene Expression ◽

Gene Expression Profile ◽

Expression Profile ◽

Active Sites ◽

Evolutionary Analysis ◽

Base Modification ◽

Binding Domains ◽

Non Coding Rna ◽

Beta Sheet Structure ◽

The Family

N1-methyladenosine (m1A) is a kind of common and abundant methylation modification in eukaryotic mRNA and long-chain non-coding RNA. Nucleoside methyltransferase (MTase) of m1A is a diverse protein family, which is characterized by the presence of methyltransferases like domains and conserved S-adenosylmethionine (SAM) binding domains formed by the central sevenstranded beta-sheet structure. However, comprehensive analysis of the gene expression profile of such enzymes has not been performed to classify them according to evolutionary criteria and to guide the functional prediction. Here, we conducted extensive searches of databases to collect all members of previously identified m1A RNA methyltransferases. And we report bioinformatics studies on gene expression profile based on evolutionary analysis, sequence alignment, expression in tissues and cells within the family of RNA methyltransferases. Our analysis showed that the base modification behavior mediated by m1A RNA methyltransferases evolved from invertebrate, and the active sites of m1A RNA methyltransferases were highly conserved during the evolution from invertebrates to human. And m1A RNA methyltransferases have low tissue and cell specificity.

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A molecular basis for transdetermination in Drosophila imaginal discs: interactions between wingless and decapentaplegic signaling

Development ◽

10.1242/dev.125.1.115 ◽

1998 ◽

Vol 125 (1) ◽

pp. 115-124

Author(s):

L. Maves ◽

G. Schubiger

Keyword(s):

Cell Fate ◽

Molecular Basis ◽

Regulatory Element ◽

Ectopic Expression ◽

Wing Development ◽

Downstream Target ◽

Leg Development ◽

Disc Cells ◽

Targeted Expression ◽

Necessary And Sufficient

We are investigating how Drosophila imaginal disc cells establish and maintain their appendage-specific determined states. We have previously shown that ectopic expression of wingless (wg) induces leg disc cells to activate expression of the wing marker Vestigial (Vg) and transdetermine to wing cells. Here we show that ectopic wg expression non-cell-autonomously induces Vg expression in leg discs and that activated Armadillo, a cytosolic transducer of the Wg signal, cell-autonomously induces Vg expression in leg discs, indicating that this Vg expression is directly activated by Wg signaling. We find that ubiquitous expression of wg in leg discs can induce only dorsal leg disc cells to express Vg and transdetermine to wing. Dorsal leg disc cells normally express high levels of decapentaplegic (dpp) and its downstream target, optomotor-blind (omb). We find that high levels of dpp expression, which are both necessary and sufficient for dorsal leg development, are required for wg-induced transdetermination. We show that dorsalization of ventral leg disc cells, through targeted expression of either dpp or omb, is sufficient to allow wg to induce Vg expression and wing fate. Thus, dpp and omb promote both dorsal leg cell fate as well as transdetermination-competent leg disc cells. Taken together, our results show that the Wg and Dpp signaling pathways cooperate to induce Vg expression and leg-towing transdetermination. We also show that a specific vg regulatory element, the vg boundary enhancer, is required for transdetermination. We propose that an interaction between Wg and Dpp signaling can explain why leg disc cells transdetermine to wing and that our results have implications for normal leg and wing development.

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Lhx2, a vertebrate homologue of apterous, regulates vertebrate limb outgrowth

Development ◽

10.1242/dev.125.20.3925 ◽

1998 ◽

Vol 125 (20) ◽

pp. 3925-3934 ◽

Cited By ~ 3

Author(s):

C. Rodriguez-Esteban ◽

J.W. Schwabe ◽

J.D. Pena ◽

D.E. Rincon-Limas ◽

J. Magallon ◽

...

Keyword(s):

Cell Fate ◽

Wing Development ◽

Dorsoventral Axis ◽

Drosophila Wing ◽

Vertebrate Limb ◽

Limb Outgrowth ◽

Necessary And Sufficient ◽

Dorsal Cell Fate

apterous specifies dorsal cell fate and directs outgrowth of the wing during Drosophila wing development. Here we show that, in vertebrates, these functions appear to be performed by two separate proteins. Lmx-1 is necessary and sufficient to specify dorsal identity and Lhx2 regulates limb outgrowth. Our results suggest that Lhx2 is closer to apterous than Lmx-1, yet, in vertebrates, Lhx2 does not specify dorsal cell fate. This implies that in vertebrates, unlike Drosophila, limb outgrowth can be dissociated from the establishment of the dorsoventral axis.

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