Browsing by Author "Sharma, Shivani"

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Dynamic role of aquaporin transport system under drought stress in plants
(Elsevier B.V., 2021) Shivaraj, SM; Sharma, Yogesh; Chaudhary, Juhi; Rajora, Nitika; Sharma, Shivani; Thakral, Vandana; Ram, Hasthi; Sonah, Humira; Singla-Pareek, Sneh L.; Sharma, Tilak Raj; Deshmukh, Rupesh
Prolonged soil moisture deficit poses major threat to plant survival. Plants have evolved to withstand such condition by maintaining water status through adoptive mechanisms. Such mechanisms include modulation of Aquaporins (AQPs) activity. The AQPs are small integral membrane proteins which facilitate water movement across the cells. This review summarizes the important regulatory mechanisms controlling the dynamics of AQP activity to fine tune the plant water status under the water deficit condition. Numerous studies have shown differential AQP expression under drought stress in plants. Among the known AQP subfamilies, members of plasma membrane intrinsic protein (PIP) and tonoplast intrinsic protein (TIP) showed most significant expression under drought condition. The activity, stability, and membrane targeting of these AQPs are known to be regulated at transcriptional as well as post-translational level. Drought induced transcription factors and hormones are also involved in direct or indirect transcriptional regulation. At post-translational level modifications such as phosphorylation, glycosylation, ubiquitination, gating and tetramerization play a role in regulation of the abundance and activity of AQP proteins. Understanding such regulatory mechanisms will help in exploration of AQPs to improve crop plants for sustainable agriculture under changing environmental conditions.
Essential role of MED1 in the transcriptional regulation of ER-dependent oncogenic miRNAs in breast cancer
(Springer Nature, 2018) Nagpal, Neha; Sharma, Shivani; Maji, Sourobh; Durante, Giorgio; Ferracin, Manuela; Thakur, Jitendra K.; Kulshreshtha, Ritu
Mediator complex has been extensively shown to regulate the levels of several protein-coding genes; however, its role in the regulation of miRNAs in humans remains unstudied so far. Here we show that MED1, a Mediator subunit in the Middle module of Mediator complex, is overexpressed in breast cancer and is a negative prognostic factor. The levels of several miRNAs (miR-100-5p, -191-5p, -193b-3p, -205-5p, -326, -422a and -425-5p) were found to be regulated by MED1. MED1 induces miR-191/425 cluster in an estrogen receptor-alpha (ER-α) dependent manner. Occupancy of MED1 on estrogen response elements (EREs) upstream of miR-191/425 cluster is estrogen and ER-α-dependent and ER-α-induced expression of these miRNAs is MED1-dependent. MED1 mediates induction of cell proliferation and migration and the genes associated with it (JUN, FOS, EGFR, VEGF, MMP1, and ERBB4) in breast cancer, which is abrogated when used together with miR-191-inhibition. Additionally, we show that MED1 also regulates the levels of direct miR-191 target genes such as SATB1, CDK6 and BDNF. Overall, the results show that MED1/ER-α/miR-191 axis promotes breast cancer cell proliferation and migration and may serve as a novel target for therapy.
The interplay of HuR and miR-3134 in regulation of AU rich transcriptome
(Taylor & Francis Group, 2013) Sharma, Shivani; Verma, Suneer; Vasudevan, Madavan; Samanta, Subhasis; Thakur, Jitendra K.; Kulshreshtha, Ritu
MicroRNAs and AU Rich element (ARE)-mediated degradation of transcripts are thought to be two independent means of gene regulation at the post-transcriptional level. However, since their site of action is the same (3'UTR of mRNA), there exists a high probability that specific miRNAs may bind to AREs and, thus, interact with ARE-binding proteins (ARE-BPs) to regulate transcript levels. In this study, we have characterized AREs as potential targets of hsa-miR-3134. An analysis of the global gene expression profile of breast cancer cell line MCF7 overexpressing miR-3134 revealed the presence of at least one AUUUA element in the 3'-UTRs of 63% of miR-3134 regulated protein coding genes. Quantitative RT-PCR or 3'UTR luciferase assays show that miR-3134 mediates an up to 4-8-fold increase in the levels of ARE bearing transcripts-SOX9, VEGFA, and EGFR, while mutated miR-3134 shows a decreased effect. The miR-3134-mediated increase in transcript levels was unaffected by treatment with transcription inhibitor (actinomycin D), indicating that miR-3134 enhances transcript stability. To investigate a possible interplay between miR-3134 and a prototype ARE-BP, HuR, we compared their overexpression transcriptome profiles. Interestingly, up to 80% of miR-3134-regulated genes were also regulated by HuR. Overexpression studies of HuR alone or in combination with miR-3134 shows that wt miR-3134 but not a mutated miR-3134 promotes stabilization of HuR-regulated transcripts SOX9, VEGFA, and EGFR as confirmed by qRT-PCR or RNA-immunoprecipitation experiments. Overall, this report suggests that collaboration between ARE-binding microRNAs and ARE-binding proteins could be a general mechanism of 3'-UTR mediated regulation of gene expression in human cells.