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Fulltext Systematic identification and characterization of Aedes aegypti long noncoding RNAs (lncRNAs)

Azlan A, Obeidat SM, Yunus MA, Azzam G

Sci Rep, 2019 08 21;9(1):12147.
PMID: 31434910 DOI: 10.1038/s41598-019-47506-9

Long noncoding RNAs (lncRNAs) play diverse roles in biological processes. Aedes aegypti (Ae. aegypti), a blood-sucking mosquito, is the principal vector responsible for replication and transmission of arboviruses including dengue, Zika, and Chikungunya virus. Systematic identification and developmental characterisation of Ae. aegypti lncRNAs are still limited. We performed genome-wide identification of lncRNAs, followed by developmental profiling of lncRNA in Ae. aegypti. We identified a total of 4,689 novel lncRNA transcripts, of which 2,064, 2,076, and 549 were intergenic, intronic, and antisense respectively. Ae. aegypti lncRNAs share many characteristics with other species including low expression, low GC content, short in length, and low conservation. Besides, the expression of Ae. aegypti lncRNAs tend to be correlated with neighbouring and antisense protein-coding genes. A subset of lncRNAs shows evidence of maternal inheritance; hence, suggesting potential role of lncRNAs in early-stage embryos. Additionally, lncRNAs show higher tendency to be expressed in developmental and temporal specific manner. The results from this study provide foundation for future investigation on the function of Ae. aegypti lncRNAs.

Matched MeSH terms: RNA, Antisense/genetics; RNA, Antisense/metabolism
Identification of novel non-coding RNAs as potential antisense regulators in the archaeon Sulfolobus solfataricus

Tang TH, Polacek N, Zywicki M, Huber H, Brugger K, Garrett R, et al.

Mol Microbiol, 2005 Jan;55(2):469-81.
PMID: 15659164

By generating a specialized cDNA library from the archaeon Sulfolobus solfataricus, we have identified 57 novel small non-coding RNA (ncRNA) candidates and confirmed their expression by Northern blot analysis. The majority was found to belong to one of two classes, either antisense or antisense-box RNAs, where the latter only exhibit partial complementarity to RNA targets. The most prominent group of antisense RNAs is transcribed in the opposite orientation to the transposase genes, encoded by insertion elements (transposons). Thus, these antisense RNAs may regulate transposition of insertion elements by inhibiting expression of the transposase mRNA. Surprisingly, the class of antisense RNAs also contained RNAs complementary to tRNAs or sRNAs (small-nucleolar-like RNAs). For the antisense-box ncRNAs, the majority could be assigned to the class of C/D sRNAs, which specify 2'-O-methylation sites on rRNAs or tRNAs. Five C/D sRNAs of this group are predicted to target methylation at six sites in 13 different tRNAs, thus pointing to the widespread role of these sRNA species in tRNA modification in Archaea. Another group of antisense-box RNAs, lacking typical C/D sRNA motifs, was predicted to target the 3'-untranslated regions of certain mRNAs. Furthermore, one of the ncRNAs that does not show antisense elements is transcribed from a repeat unit of a cluster of small regularly spaced repeats in S. solfataricus which is potentially involved in replicon partitioning. In conclusion, this is the first report of stably expressed antisense RNAs in an archaeal species and it raises the prospect that antisense-based mechanisms are also used widely in Archaea to regulate gene expression.

Matched MeSH terms: RNA, Antisense/genetics*
Resolution of coronavirus disease 2019 (COVID-19)

Habas K, Nganwuchu C, Shahzad F, Gopalan R, Haque M, Rahman S, et al.

Expert Rev Anti Infect Ther, 2020 12;18(12):1201-1211.
PMID: 32749914 DOI: 10.1080/14787210.2020.1797487

INTRODUCTION: Coronavirus disease 2019 (COVID-19) was first detected in China in December, 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. The effective option of antiviral therapy and vaccination are currently under evaluation and development.
AREAS COVERED: A literature search was performed using PubMed between December 1, 2019-June 23, 2020. This review highlights the current state of knowledge on the viral replication and pathogenicity, diagnostic and therapeutic strategies, and management of COVID-19. This review will be of interest to scientists and clinicians and make a significant contribution toward development of vaccines and targeted therapies to contain the pandemic.
EXPERT OPINION: The exit strategy for a path back to normal life is required, which should involve a multi-prong effort toward development of new treatment and a successful vaccine to protect public health worldwide and prevent future COVID-19 outbreaks. Therefore, the bench to bedside translational research as well as reverse translational works focusing bedside to bench is very important and would provide the foundation for the development of targeted drugs and vaccines for COVID-19 infections.

Matched MeSH terms: RNA, Antisense/therapeutic use
Fulltext Derivation of an endogenous small RNA from double-stranded Sox4 sense and natural antisense transcripts in the mouse brain

Ling KH, Brautigan PJ, Moore S, Fraser R, Cheah PS, Raison JM, et al.

Genomics, 2016 Mar;107(2-3):88-99.
PMID: 26802803 DOI: 10.1016/j.ygeno.2016.01.006

Natural antisense transcripts (NATs) are involved in cellular development and regulatory processes. Multiple NATs at the Sox4 gene locus are spatiotemporally regulated throughout murine cerebral corticogenesis. In the study, we evaluated the potential functional role of Sox4 NATs at Sox4 gene locus. We demonstrated Sox4 sense and NATs formed dsRNA aggregates in the cytoplasm of brain cells. Over expression of Sox4 NATs in NIH/3T3 cells generally did not alter the level of Sox4 mRNA expression or protein translation. Upregulation of a Sox4 NAT known as Sox4ot1 led to the production of a novel small RNA, Sox4_sir3. Its biogenesis is Dicer1-dependent and has characteristics resemble piRNA. Expression of Sox4_sir3 was observed in the marginal and germinative zones of the developing and postnatal brains suggesting a potential role in regulating neurogenesis. We proposed that Sox4 sense-NATs serve as Dicer1-dependent templates to produce a novel endo-siRNA- or piRNA-like Sox4_sir3.

Matched MeSH terms: RNA, Antisense/genetics*; RNA, Antisense/metabolism
Fulltext Bcl-xL silencing induces alterations in hsa-miR-608 expression and subsequent cell death in A549 and SK-LU1 human lung adenocarcinoma cells

Othman N, In LL, Harikrishna JA, Hasima N

PLoS One, 2013;8(12):e81735.
PMID: 24339958 DOI: 10.1371/journal.pone.0081735

Bcl-xL is an anti-apoptotic protein that is frequently found to be overexpressed in non-small cell lung cancer leading to an inhibition of apoptosis and poor prognosis. Recently, the role of miRNAs in regulating apoptosis and cell survival during tumorigenesis has become evident, with cancer cells showing perturbed expression of various miRNAs. In this study, we utilized miRNA microarrays to determine if miRNA dysregulation in bcl-xL silenced lung adenocarcinoma cells could be involved in regulating cell death. Short interfering RNA-based transfection of A549 and SK-LU1 lung adenocarcinoma cells was successful in inducing a reduction in bcl-xL expression levels, resulting in a decrease in cell viability. A total of 10 miRNAs were found to be significantly differentially expressed when compared between siRNA-transfected and non-transfected cells including hsa-miR-181a, hsa-miR-769-5p, hsa-miR-361-5p, hsa-miR-1304 and hsa-miR-608. When overexpression studies on hsa-miR-608 was performed via transfection of miRNA mimics, cell death was found to be induced in A549 and SK-LU1 cells in comparison to untreated cells. This effect was reversed when knockdown studies involving anti-sense inhibitors were introduced. Combination of siRNA based silencing of bcl-xL (siBcl-xL) followed by anti-sense inhibitor transfection led to a decrease in the apoptotic population of A549 and SK-LU1 cells in comparison to cells only treated with siBcl-xL, illustrating the connection between bcl-xL, hsa-miR-608 and cell death. Gene target prediction analysis implicated the PI3K/AKT, WNT, TGF-β, and ERK signaling pathways as targets of bcl-xL induced miRNA alterations. We have demonstrated that bcl-xL silencing in A549 and SK-LU1 cells leads to the occurrence of cell death through the dysregulation of specific miRNAs. This study also provides a platform for anti-sense gene therapy whereby miRNA expression can be exploited to increase the apoptotic properties in lung adenocarcinoma cells.

Matched MeSH terms: RNA, Antisense/genetics