During aging, organisms show altered gene expression patterns and have an increasingly impaired ability to respond to stress-causing and mitogenic stimuli. Since post-transcriptional processes critically regulate changes in the collections of expressed proteins, the role of RBPs (described in other projects) and noncoding RNAs (particularly microRNAs and lncRNAs) are emerging as major factors controlling age-related gene expression patterns. To investigate ncRNA function during senescence, we employ approaches such as ncRNA reduction (by transfecting an antisense molecules), ncRNA overexpression (by transfecting precursors or mature ncRNA molecules), and identification of ncRNA-associated mRNAs by tagging the ncRNAs (using biotin or MS2 tags) and identifying target mRNAs through various methods (eg, microarray, RT-PCR). We investigate whether ncRNAs affect the stability of target mRNAs during senescence by measuring the steady-state levels and half-lives of the mRNAs of interest as a function of ncRNA abundance. We investigate whether ncRNAs affect the translation of target mRNAs by modulating ncRNA levels, and subsequently studying the relative association of the mRNA with translating polysomes and by quantifying the nascent translation rates of the encoded proteins. We also employ reporter constructs to gain additional insight into the processes modulated by ncRNAs and use different senescence-associated markers to examine changes in the senescence phenotype. During the past funding period, we have reported that the senescence-associated microRNA miR-519 plays a central role in autophagy (Abdelmohsen et al., Mol. Cell Biol, 2012), that miR-130 suppresses adipogenesis by lowering PPAR production (Lee et al., Mol. Cell Biol, 2011), and that miR-146 inhibits brain metastases (Hwang et al., Molecules and Cells, 2012). We have also shown that expression of a senescence-upregulated lncRNA (lincRNA-p21) is inhibited by the microRNA let-7 (Yoon et al., Mol. Cell 2012) and that a general factor in the production of microRNAs (Drosha) is inhibited by the senescence-downregulated protein AUF1 (Abdelmohsen et al., 2012). We reviewed the contributions of microRNAs in senescence and aging in several articles (Srikantan et al., Cell Cycle, 2011;Abdelmohsen and Gorospe, 2011;Srikantan et al., Cell Cycle, 2011) as well as in one book chapter (Grammatikakis and Gorospe, in MicroRNAs in Medicine 2012).
| Kim, Kyoung Mi; Abdelmohsen, Kotb; Mustapic, Maja et al. (2017) RNA in extracellular vesicles. Wiley Interdiscip Rev RNA 8: |
| Kim, Kyoung Mi; Noh, Ji Heon; Abdelmohsen, Kotb et al. (2017) Mitochondrial noncoding RNA transport. BMB Rep 50:164-174 |
| Noh, Ji Heon; Kim, Kyoung Mi; Abdelmohsen, Kotb et al. (2016) HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP. Genes Dev 30:1224-39 |
| Kim, Jiyoung; Kim, Kyoung Mi; Noh, Ji Heon et al. (2016) Long noncoding RNAs in diseases of aging. Biochim Biophys Acta 1859:209-21 |
| Lastres-Becker, Isabel; Nonis, David; Eich, Florian et al. (2016) Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K/mTOR and is induced by starvation. Biochim Biophys Acta 1862:1558-69 |
| Scheibye-Knudsen, Morten; Tseng, Anne; Borch Jensen, Martin et al. (2016) Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA. Proc Natl Acad Sci U S A 113:12502-12507 |
| Di Francesco, Andrea; Di Germanio, Clara; Panda, Amaresh C et al. (2016) Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation. Free Radic Biol Med 99:225-233 |
| Panda, Amaresh C; Abdelmohsen, Kotb; Martindale, Jennifer L et al. (2016) Novel RNA-binding activity of MYF5 enhances Ccnd1/Cyclin D1 mRNA translation during myogenesis. Nucleic Acids Res 44:2393-408 |
| Kim, Chongtae; Lee, Heejin; Kang, Hoin et al. (2016) RNA-binding protein HuD reduces triglyceride production in pancreatic ? cells by enhancing the expression of insulin-induced gene 1. Biochim Biophys Acta 1859:675-85 |
| Lee, Kwang-Pyo; Shin, Yeo Jin; Panda, Amaresh C et al. (2015) miR-431 promotes differentiation and regeneration of old skeletal muscle by targeting Smad4. Genes Dev 29:1605-17 |
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