YY1 binds to α-synuclein 3′-flanking region SNP and stimulates antisense noncoding RNA expression

Mizuta, Ikuko; Takafuji, Kazuaki; Ando, Yuko; Satake, Wataru; Kanagawa, Motoi; Kobayashi, Kazuhiro; Nagamori, Shushi; Shinohara, Takayuki; Ito, Chiyomi; Yamamoto, Mitsutoshi; Hattori, Nobutaka; Murata, Miho; Kanai, Yoshikatsu; Murayama, Shigeo; Nakagawa, Masanori; Toda, Tatsushi
November 2013
Journal of Human Genetics;Nov2013, Vol. 58 Issue 11, p711
Academic Journal
α-synuclein (SNCA) is an established susceptibility gene for Parkinson's disease (PD), one of the most common human neurodegenerative disorders. Increased SNCA is considered to lead to PD and dementia with Lewy bodies. Four single-nucleotide polymorphisms (SNPs) in SNCA 3′ region were prominently associated with PD among different ethnic groups. To examine how these SNPs influence disease susceptibility, we analyzed their potential effects on SNCA gene expression. We found that rs356219 showed allele-specific features. Gel shift assay using nuclear extracts from SH-SY5Y cells showed binding of one or more proteins to the protective allele, rs356219-A. We purified the rs356219-A-protein complex with DNA affinity beads and identified a bound protein using mass spectrometry. This protein, YY1 (Yin Yang 1), is an ubiquitous transcription factor with multiple functions. We next investigated SNCA expression change in SH-SY5Y cells by YY1 transfection. We also analyzed the expression of antisense noncoding RNA (ncRNA) RP11-115D19.1 in SNCA 3′-flanking region, because rs356219 is located in intron of RP11-115D19.1. Little change was observed in SNCA expression levels; however, RP11-115D19.1 expression was prominently stimulated by YY1. In autopsied cortices, positive correlation was observed among RP11-115D19.1, SNCA and YY1 expression levels, suggesting their functional interactions in vivo. Knockdown of RP11-115D19.1 increased SNCA expression significantly in SH-SY5Y cells, suggesting its repressive effect on SNCA expression. Our findings of the protective allele-specific YY1 and antisense ncRNA raised a novel possible mechanism to regulate SNCA expression.


Related Articles

  • Transcripts of a heterologous gene encoding mite allergen Der f 7 are stabilized by codon optimization in Aspergillus oryzae. Tanaka, Mizuki; Tokuoka, Masafumi; Shintani, Takahiro; Gomi, Katsuya // Applied Microbiology & Biotechnology;Dec2012, Vol. 96 Issue 5, p1275 

    We have previously demonstrated that transcripts of an AT-biased heterologous gene encoding mite allergen Der f 7 from Dermatophagoides farinae were polyadenylated prematurely within the coding region when native cDNA was expressed in Aspergillus oryzae, and that this premature polyadenylation...

  • A platform independent RNA-Seq protocol for the detection of transcriptome complexity. Calabrese, Claudia; Mangiulli, Marina; Manzari, Caterina; Paluscio, Anna Maria; Caratozzolo, Mariano Francesco; Marzano, Flaviana; Kurelac, Ivana; D'Erchia, Anna Maria; D'Elia, Domenica; Licciulli, Flavio; Liuni, Sabino; Picardi, Ernesto; Attimonelli, Marcella; Gasparre, Giuseppe; Porcelli, Anna Maria; Pesole, Graziano; Sbisà, Elisabetta; Tullo, Apollonia // BMC Genomics;2013, Vol. 14 Issue 1, p1 

    Background Recent studies have demonstrated an unexpected complexity of transcription in eukaryotes. The majority of the genome is transcribed and only a little fraction of these transcripts is annotated as protein coding genes and their splice variants. Indeed, most transcripts are the result...

  • Cloning of the cDNA encoding adenosine 5′-monophosphate deaminase 1 and its mRNA expression in Japanese flounder Paralichthys olivaceus. Jiang, Keyong; Sun, Shujuan; Liu, Mei; Wang, Baojie; Meng, Xiaolin; Wang, Lei // Chinese Journal of Oceanology & Limnology;Jan2013, Vol. 31 Issue 1, p118 

    AMP deaminase catalyzes the conversion of AMP into IMP and ammonia. In the present study, a full-length cDNA of AMPD1 from skeletal muscle of Japanese flounder Paralichthys olivaceus was cloned and characterized. The 2 526 bp cDNA contains a 5′-UTR of 78 bp, a 3′-UTR of 237 bp and an...

  • Na+/K+-ATPase α-subunit (nkaα) Isoforms and Their mRNA Expression Levels, Overall Nkaα Protein Abundance, and Kinetic Properties of Nka in the Skeletal Muscle and Three Electric Organs of the Electric Eel, Electrophorus electricus. Ching, Biyun; Woo, Jia M.; Hiong, Kum C.; Boo, Mel V.; Choo, Celine Y. L.; Wong, Wai P.; Chew, Shit F.; Ip, Yuen K. // PLoS ONE;Mar2015, Vol. 10 Issue 3, p1 

    This study aimed to obtain the coding cDNA sequences of Na+/K+-ATPase α (nkaα) isoforms from, and to quantify their mRNA expression in, the skeletal muscle (SM), the main electric organ (EO), the Hunter’s EO and the Sach’s EO of the electric eel, Electrophorus electricus....

  • The transcript catalogue of the short-lived fish Nothobranchius furzeri provides insights into age-dependent changes of mRNA levels. Petzold, Andreas; Reichwald, Kathrin; Groth, Marco; Taudien, Stefan; Hartmann, Nils; Priebe, Steffen; Shagin, Dmitry; Englert, Christoph; Platzer, Matthias // BMC Genomics;2013, Vol. 14 Issue 1, p1 

    Background: The African annual fish Nothobranchius furzeri has over recent years been established as a model species for ageing-related studies. This is mainly based on its exceptionally short lifespan and the presence of typical characteristics of vertebrate ageing. To substantiate its role as...

  • Partial Optimization of the 5-Terminal Codon Increased a Recombination Porcine Pancreatic Lipase (opPPL) Expression in Pichia pastoris. Zhao, Hua; Chen, Dan; Tang, Jiayong; Jia, Gang; Long, Dingbiao; Liu, Guangmang; Chen, Xiaoling; Shang, Haiying // PLoS ONE;Dec2014, Vol. 9 Issue 12, p1 

    Pancreatic lipase plays a key role in intestinal digestion of feed fat, and is often deficient in young animals such as weaning piglets. The objective of this study was to express and characterize a partial codon optimized porcine pancreatic lipase (opPPL). A 537 bp cDNA fragment encoding...

  • Therapeutic Applications of Antisense Oligonucleotides in Asthma and Allergy. Isidoro-Garc�a, Mar�a; D�vila, Ignacio // Recent Patents on Inflammation & Allergy Drug Discovery;Nov2007, Vol. 1 Issue 3, p171 

    Antisense oligonucleotides represent a novel therapeutic approach for manipulation of gene expression in the treatment of respiratory diseases. This methodology is based on the use of synthetic oligonucleotides to inhibit the expression of a specific target gene by inhibiting the function of the...

  • Subgroup-specific alternative splicing in medulloblastoma. Dubuc, Adrian; Morrissy, A.; Kloosterhof, Nanne; Northcott, Paul; Yu, Emily; Shih, David; Peacock, John; Grajkowska, Wieslawa; Meter, Timothy; Eberhart, Charles; Pfister, Stefan; Marra, Marco; Weiss, William; Scherer, Stephen; Rutka, James; French, Pim; Taylor, Michael // Acta Neuropathologica;Apr2012, Vol. 123 Issue 4, p485 

    Medulloblastoma comprises four distinct molecular variants: WNT, SHH, Group 3, and Group 4. We analyzed alternative splicing usage in 14 normal cerebellar samples and 103 medulloblastomas of known subgroup. Medulloblastoma samples have a statistically significant increase in alternative splicing...

  • Use of the Polymerase Chain Reaction in Quantification of Interleukin 8 mRNA in Minute Epidermal Samples. Paludan, Kirsten; Thestrup-Pedersen, Kristian // Journal of Investigative Dermatology;Dec92, Vol. 99 Issue 6, p830 

    Quantitative studies of cytokine gene expression in vivo are necessary in order to properly describe the cytokine network and to elucidate its role in skin inflammation. Ideally, one should be able to follow cytokine gene expression in epidermal, dermal, and blood compartments. However,...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics