organelle network biology seminar series...directly with the poly(a) tails of rna transcripts to...

場 所 生命機能研究科 ナノバイオロジー棟 3階 セミナー室 日 時 6 20 日(月) 17:00-18:00 Mutation of the Gene Encoding an Evolutionarily Conserved Polyadenosine RNA Binding Protein that Controls Poly(A) Tail Length Lead to Intellectual Disability in Humans and Neuronal Dysfunction in Flies ■ 問い合わせ先 / 大阪大学 大学院生命機能研究科 細胞内分子移動学研究室 [email protected] 「オルガネラネットワーク医学創成プログラム」 大阪大学 グローバルCOE 大阪大学 グローバルCOE Post-transcriptional processing of RNA plays a critical role in controlling gene expression thus influencing the fate and function of each cell. These post-transcriptional events are mediated by numerous RNA binding proteins that associate with mRNA transcript from the time that they are made in the nucleus until they meet their demise in the cytoplasm. Poly(A) bindings proteins also known as Pabs comprise one class of RNA binding proteins that associate directly with the poly(A) tails of RNA transcripts to modulate polyadenylation and export from the nucleus as well as translation and transcript stability. Like other RNA processing factors, Pabs are highly conserved through evolution. While most Pabs bind to RNA via RNA Recognition Motifs (RRMs), we recently identified an evolutionarily conserved family of CysCysCysHis zinc finger Pabs typified by the essential S. cerevisiae protein, Nab2. Nab2 is an essential budding yeast protein that is localized to the nucleus where it associates with the poly(A) tail of mRNA transcripts and plays roles in polyadenylation and export. Our studies of Nab2 have provided insights into how Nab2 contributes to preferential export of properly processed RNA to the cytoplasm and studies are ongoing to understand how Nab2 limits poly(A) tail length. We have recently extended our work of Nab2 to understand tissue-specific functions in multi-cellular model systems including Drosophila and mice. These studies were catalyzed by the finding that the human counterpart of Nab2, ZC3H14, is mutated in patients with a form of nonsyndromic autosomal recessive intellectual disability. Our studies in Drosophila now reveal key roles for Drosophila Nab2 (dNab2) in neurons. We are combining studies in model systems as well as cultured patient cells and neurons to understand how Nab2/ZC3H14 influences post-transcriptional events and thus contributes to human disease. Anita H. Corbett  博士 Professor of Biochemistry, Emory University School of Medicine

Upload: others

Post on 09-Jul-2020

3 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Organelle Network Biology Seminar Series...directly with the poly(A) tails of RNA transcripts to modulate polyadenylation and export from the nucleus as well as translation and transcript

場 所 生命機能研究科 ナノバイオロジー棟 3階 セミナー室日 時 6月20日(月) 17:00-18:00

Org

anell

e Net

wor

k B

iolo

gy S

emin

ar S

eries

Org

anell

e Net

wor

k B

iolo

gy S

emin

ar S

eries

Org

anell

e Net

wor

k B

iolo

gy S

emin

ar S

eries

Mutation of the Gene Encoding an Evolutionarily Conserved Polyadenosine RNA Binding Protein that Controls Poly(A) Tail Length Lead to Intellectual Disability in Humans and Neuronal Dysfunction in Flies

■ 問い合わせ先 / 大阪大学 大学院生命機能研究科 細胞内分子移動学研究室 [email protected]

「オルガネラネットワーク医学創成プログラム」大阪大学 グローバルCOE大阪大学 グローバルCOE

Post-transcriptional processing of RNA plays a critical role in controlling gene expression thus influencing the fate and function of each cell. These post-transcriptional events are mediated by numerous RNA binding proteins that associate with mRNA transcript from the time that they are made in the nucleus until they meet their demise in the cytoplasm. Poly(A) bindings proteins also known as Pabs comprise one class of RNA binding proteins that associate directly with the poly(A) tails of RNA transcripts to modulate polyadenylation and export from the nucleus as well as translation and transcript stability. Like other RNA processing factors, Pabs are highly conserved through evolution. While most Pabs bind to RNA via RNA Recognition Motifs (RRMs), we recently identified an evolutionarily conserved family of CysCysCysHis zinc finger Pabs typified by the essential S. cerevisiae protein, Nab2. Nab2 is an essential budding yeast protein that is localized to the nucleus where it associates with the poly(A) tail of mRNA transcripts and plays roles in polyadenylation and export. Our studies of Nab2 have provided insights into how Nab2 contributes to preferential export of properly processed RNA to the cytoplasm and studies are ongoing to understand how Nab2 limits poly(A) tail length. We have recently extended our work of Nab2 to understand tissue-specific functions in multi-cellular model systems including Drosophila and mice. These studies were catalyzed by the finding that the human counterpart of Nab2, ZC3H14, is mutated in patients with a form of nonsyndromic autosomal recessive intellectual disability. Our studies in Drosophila now reveal key roles for Drosophila Nab2 (dNab2) in neurons. We are combining studies in model systems as well as cultured patient cells and neurons to understand how Nab2/ZC3H14 influences post-transcriptional events and thus contributes to human disease.

Anita H. Corbett 博士Professor of Biochemistry, Emory University School of Medicine

1105-0985_大阪大学オルガネラネットワーク バイオロジーセミナー6月20日