MicroRNA Implications across Neurodevelopment and Neuropathology

Martino, Sabata; Girolamo, Ilaria di; Orlacchio, Antonio; Datti, Alessandro; Orlacchio, Aldo

doi:10.1155/2009/654346

Cited by 51 publications

(47 citation statements)

References 203 publications

(192 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…apoptosis (36,37), tumorigenesis (38,39), and many other physiological or pathological processes (40,41). Notably, the first identified target for miR-340 was microphthalmia-associated transcription factor (MITF), which is a master regulator of melanocyte development and melanogenesis in melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA 340 Is Involved in UVB-Induced Dendrite Formation through the Regulation of RhoA Expression in Melanocytes

Jin

Zhu

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

The influence of UV irradiation on pigmentation is well established, but the molecular and cellular mechanisms controlling dendrite formation remain incompletely understood. MicroRNAs (miRNAs) are a class of small RNAs that participate in various cellular processes by suppressing the expression of target mRNAs. In this study, we investigated the expression of miRNAs in response to UVB irradiation using a microarray screen and then identified potential mRNA targets for differentially expressed miRNAs among the genes governing dendrite formation. We subsequently determined the ability of miRNA 340 (miR-340) to suppress the expression of RhoA, which is a predicted miR-340 target gene that regulates dendrite formation. The overexpression of miR-340 promoted dendrite formation and melanosome transport, and the downregulation of miR-340 inhibited UVBinduced dendrite formation and melanosome transport. Moreover, a luciferase reporter assay demonstrated direct targeting of RhoA by miR-340 in the immortalized human melanocyte cell line Pig1. In conclusion, this study has established an miRNA associated with UVB irradiation. The significant downregulation of RhoA protein and mRNA expression after UVB irradiation and the modulation of miR-340 expression suggest a key role for miR-340 in regulating UVB-induced dendrite formation and melanosome transport. Melanocytes originate from neural crest-derived melanoblasts, which migrate and differentiate in the basal layer of the epidermis (1). A hallmark of melanocytes is their ability to form dendrites, which are specialized cell structures that transport melanosomes to their tips for transfer to the surrounding keratinocytes in response to growth factors and UV irradiation. Following skin penetration by UV rays and subsequent DNA damage, thymidine dinucleotide fragments induce melanogenesis and cause the melanocyte to produce melanosomes (2).These melanosomes are then transferred to neighboring keratinocytes through the intricate network of melanocyte dendrites, contributing to skin darkening and thereby providing protection from UV radiation (3, 4). Melanocyte dendrites can vary markedly in length and number in response to different growth factors and, in a manner analogous to the way in which neural cells seek out target neurons, these dendrites form growth cone-like structures that attach to keratinocytes. Melanocyte-keratinocyte adhesion is a prerequisite for the transfer of melanosomes to keratinocytes; therefore, the formation of melanocyte dendrites, particularly of the appropriate length and number, is essential for efficient melanosome transfer. Due to the importance of dendricity for melanocyte activity, cutaneous pigmentation, and photoprotection, it is critical to determine the precise mechanisms involved in the regulation of melanocyte dendrite formation.It is well known that melanocytes are sensitive to UV irradiation, with substantial evidence suggesting that it plays a pivotal role in regulating melanocyte dendricity. Studies have shown that UV irradiation induce...

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA 340 Is Involved in UVB-Induced Dendrite Formation through the Regulation of RhoA Expression in Melanocytes

Jin

Zhu

et al. 2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Although miRNA expression profiling in nervous system is really challenging and difficult because of sampling procedures, a great number of miRNAs appear to be involved at various stages of synaptic development named as miR-132, miR-134, miR-124 and miR-138 (Martino et al, 2009;Schratt, 2009). Since synaptic formation is a process in which neurons are involved and connected to perform their roles in neurological pathways; therefore, it sounds logical that some miRNAs are specifically linked to some neurodegenerative disorders.…”

Section: Mirnas and Neurodegenerative Diseasesmentioning

confidence: 99%

MiRNA Molecular Profiles in Human Medical Conditions: Connecting Lung Cancer and Lung Development Phenomena

Aghanoori¹,

Mirzaei²,

Tavallaei³

2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

MiRNAs are endogenous, single stranded ~22-nucleotide non-coding RNAs (ncRNAs) which are transcribed by RNA polymerase II and mediate negative post-transcriptional gene regulation through binding to 3'untranslated regions (UTR), possibly open reading frames (ORFs) or 5'UTRs of target mRNAs. MiRNAs are involved in the normal physiology of eukaryotic cells, so dysregulation may be associated with diseases like cancer, and neurodegenerative, heart and other disorders. Among all cancers, lung cancer, with high incidence and mortality worldwide, is classified into two main groups: non-small cell lung cancer and small cell lung cancer. Recent promising studies suggest that gene expression profiles and miRNA signatures could be a useful step in a noninvasive, low-cost and repeatable screening process of lung cancer. Similarly, every stage of lung development during fetal life is associated with specific miRNAs. Since lung development and lung cancer phenomena share the same physiological, biological and molecular processes like cell proliferation, development and shared mRNA or expression regulation pathways, and according to data adopted from various studies, they may have partially shared miRNA signature. Thus, focusing on lung cancer in relation to lung development in miRNA studies might provide clues for lung cancer diagnosis and prognosis.

show abstract

“…Dysregulation of miRNA expression has been described in several human neurodevelopmental diseases (Martino et al 2009;Xu et al 2010;Feng and Feng 2011;Nowak and Michlewski 2013). For example, Xu et al (2008) demonstrated that miR124a ectopic expression decreases dendritic branching, an effect rescued by the loss of dFMRP expression.…”

mentioning

confidence: 99%

“…An important second way by which miRNAs may alter adult learning and memory is through neurodevelopmental roles (Xu et al 2010;Im and Kenny 2012;Saab and Mansuy 2014). Dysregulation of miRNA expression has been described in several human neurodevelopmental diseases (Martino et al 2009;Xu et al 2010;Feng and Feng 2011;Nowak and Michlewski 2013). For example, Xu et al (2008) demonstrated that miR124a ectopic expression decreases dendritic branching, an effect rescued by the loss of dFMRP expression.…”

mentioning

confidence: 99%

microRNAs That Promote or Inhibit Memory Formation in Drosophila melanogaster

et al. 2015

View full text Add to dashboard Cite

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally. Prior studies have shown that they regulate numerous physiological processes critical for normal development, cellular growth control, and organismal behavior. Here, we systematically surveyed 134 different miRNAs for roles in olfactory learning and memory formation using "sponge" technology to titrate their activity broadly in the Drosophila melanogaster central nervous system. We identified at least five different miRNAs involved in memory formation or retention from this large screen, including miR-9c, miR-31a, miR-305, miR-974, and miR-980. Surprisingly, the titration of some miRNAs increased memory, while the titration of others decreased memory. We performed more detailed experiments on two miRNAs, miR-974 and miR-31a, by mapping their roles to subpopulations of brain neurons and testing the functional involvement in memory of potential mRNA targets through bioinformatics and a RNA interference knockdown approach. This screen offers an important first step toward the comprehensive identification of all miRNAs and their potential targets that serve in gene regulatory networks important for normal learning and memory.KEYWORDS genetic screen; learning; memory; Drosophila; miRNA I NVOLVED in post-transcriptional gene regulation, microRNAs (miRNAs) are a class of small noncoding RNAs (Bushati and Cohen 2007). Prior studies have shown that they serve numerous biological processes, ranging from development to tumorigenesis (Esquela-Kerscher and Slack 2006;Kloosterman and Plasterk 2006;Krützfeldt and Stoffel 2006;Chang and Mendell 2007). miRNAs are transcribed as primary miRNAs (pri-miRNAs) from isolated genes or the introns of protein-coding genes ("mirtrons") (Filipowicz et al. 2008). miRNAs are under regulatory influences similar to protein-coding genes (Krol et al. 2010). The pri-miRNAs are then cleaved into precursor miRNAs (pre-miRNAs) by the microprocessor Drosha/Pasha protein complex and transported into the cytoplasm by Exportin5 where they mature through the Dicer/Loquacious protein complex into 21-to 24-nucleotide miRNA hairpins. These hairpins are subsequently assembled with Argonaute-containing protein complexes that bind to specific sequences on target messenger RNAs (mRNAs) using primarily a 2-to 8-nucleotide seed region (Bartel 2009). The small size of the target site allows many mRNAs to be recognized and coregulated by each individual miRNA (Bartel 2009). The miRNA complex, once bound, induces post-transcriptional silencing by translational repression and/or mRNA degradation (Filipowicz et al. 2008;Bazzini et al. 2012;Djuranovic et al. 2012).One important biological process that is understudied relative to miRNA function is learning and memory formation. Among the several known epigenetic processes that allow the nervous system to adapt to environmental signals, the miRNA system is thought to provide relatively rapid and analog control in both time and space over the expression of genomic co...

show abstract

MicroRNA Implications across Neurodevelopment and Neuropathology

Cited by 51 publications

References 203 publications

MicroRNA 340 Is Involved in UVB-Induced Dendrite Formation through the Regulation of RhoA Expression in Melanocytes

MicroRNA 340 Is Involved in UVB-Induced Dendrite Formation through the Regulation of RhoA Expression in Melanocytes

MiRNA Molecular Profiles in Human Medical Conditions: Connecting Lung Cancer and Lung Development Phenomena

microRNAs That Promote or Inhibit Memory Formation in Drosophila melanogaster

Contact Info

Product

Resources

About