A novel snRNA-like transcript affects amyloidogenesis and cell cycle progression through perturbation of Fe65L1 (APBB2) alternative splicing

Ilaria Penna, Irene Vassallo, Mario Nizzari, Debora Russo, Delfina Costa, Paola Menichini, Alessandro Poggi, Claudio Russo, Giorgio Dieci, Tullio Florio, Ranieri Cancedda, Aldo Pagano

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

FE65 proteins constitute a family of adaptors which modulates the processing of amyloid precursor protein and the consequent amyloid β production. Thus, they have been involved in the complex and partially unknown cascade of reactions at the base of Alzheimer's disease etiology. However, FE65 and FE65-like proteins may be linked to neurodegeneration through the regulation of cell cycle in post-mitotic neurons. In this work we disclose novel molecular mechanisms by which APBB2 can modulate APP processing. We show that APBB2 mRNA splicing, driven by the over-expression of a novel non-coding RNA named 45A, allow the generation of alternative protein forms endowed with differential effects on Aβ production, cell cycle control, and DNA damage response. 45A overexpression also favors cell transformation and tumorigenesis leading to a marked increase of malignancy of neuroblastoma cells. Therefore, our results highlight a novel regulatory pathway of considerable interest linking APP processing with cell cycle regulation and DNA-surveillance systems, that may represent a molecular mechanism to induce neurodegeneration in post-mitotic neurons.

Original languageEnglish
Pages (from-to)1511-1526
Number of pages16
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number6
DOIs
Publication statusPublished - Jun 2013

Fingerprint

Small Nuclear RNA
Alternative Splicing
Cell Cycle
Neurons
Untranslated RNA
Proteins
Amyloid beta-Protein Precursor
Cell Cycle Checkpoints
Neuroblastoma
Amyloid
DNA Damage
Alzheimer Disease
Carcinogenesis
Messenger RNA
DNA
Neoplasms

Keywords

  • β amyloid
  • APBB2 alternative splicing
  • Cell cycle progression non-coding RNA
  • Neurodegeneration
  • RNA polymerase III

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

A novel snRNA-like transcript affects amyloidogenesis and cell cycle progression through perturbation of Fe65L1 (APBB2) alternative splicing. / Penna, Ilaria; Vassallo, Irene; Nizzari, Mario; Russo, Debora; Costa, Delfina; Menichini, Paola; Poggi, Alessandro; Russo, Claudio; Dieci, Giorgio; Florio, Tullio; Cancedda, Ranieri; Pagano, Aldo.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1833, No. 6, 06.2013, p. 1511-1526.

Research output: Contribution to journalArticle

Penna, Ilaria ; Vassallo, Irene ; Nizzari, Mario ; Russo, Debora ; Costa, Delfina ; Menichini, Paola ; Poggi, Alessandro ; Russo, Claudio ; Dieci, Giorgio ; Florio, Tullio ; Cancedda, Ranieri ; Pagano, Aldo. / A novel snRNA-like transcript affects amyloidogenesis and cell cycle progression through perturbation of Fe65L1 (APBB2) alternative splicing. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2013 ; Vol. 1833, No. 6. pp. 1511-1526.
@article{3ce5a9ba72204b95a6d87b93846bdf3a,
title = "A novel snRNA-like transcript affects amyloidogenesis and cell cycle progression through perturbation of Fe65L1 (APBB2) alternative splicing",
abstract = "FE65 proteins constitute a family of adaptors which modulates the processing of amyloid precursor protein and the consequent amyloid β production. Thus, they have been involved in the complex and partially unknown cascade of reactions at the base of Alzheimer's disease etiology. However, FE65 and FE65-like proteins may be linked to neurodegeneration through the regulation of cell cycle in post-mitotic neurons. In this work we disclose novel molecular mechanisms by which APBB2 can modulate APP processing. We show that APBB2 mRNA splicing, driven by the over-expression of a novel non-coding RNA named 45A, allow the generation of alternative protein forms endowed with differential effects on Aβ production, cell cycle control, and DNA damage response. 45A overexpression also favors cell transformation and tumorigenesis leading to a marked increase of malignancy of neuroblastoma cells. Therefore, our results highlight a novel regulatory pathway of considerable interest linking APP processing with cell cycle regulation and DNA-surveillance systems, that may represent a molecular mechanism to induce neurodegeneration in post-mitotic neurons.",
keywords = "β amyloid, APBB2 alternative splicing, Cell cycle progression non-coding RNA, Neurodegeneration, RNA polymerase III",
author = "Ilaria Penna and Irene Vassallo and Mario Nizzari and Debora Russo and Delfina Costa and Paola Menichini and Alessandro Poggi and Claudio Russo and Giorgio Dieci and Tullio Florio and Ranieri Cancedda and Aldo Pagano",
year = "2013",
month = "6",
doi = "10.1016/j.bbamcr.2013.02.020",
language = "English",
volume = "1833",
pages = "1511--1526",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "Elsevier",
number = "6",

}

TY - JOUR

T1 - A novel snRNA-like transcript affects amyloidogenesis and cell cycle progression through perturbation of Fe65L1 (APBB2) alternative splicing

AU - Penna, Ilaria

AU - Vassallo, Irene

AU - Nizzari, Mario

AU - Russo, Debora

AU - Costa, Delfina

AU - Menichini, Paola

AU - Poggi, Alessandro

AU - Russo, Claudio

AU - Dieci, Giorgio

AU - Florio, Tullio

AU - Cancedda, Ranieri

AU - Pagano, Aldo

PY - 2013/6

Y1 - 2013/6

N2 - FE65 proteins constitute a family of adaptors which modulates the processing of amyloid precursor protein and the consequent amyloid β production. Thus, they have been involved in the complex and partially unknown cascade of reactions at the base of Alzheimer's disease etiology. However, FE65 and FE65-like proteins may be linked to neurodegeneration through the regulation of cell cycle in post-mitotic neurons. In this work we disclose novel molecular mechanisms by which APBB2 can modulate APP processing. We show that APBB2 mRNA splicing, driven by the over-expression of a novel non-coding RNA named 45A, allow the generation of alternative protein forms endowed with differential effects on Aβ production, cell cycle control, and DNA damage response. 45A overexpression also favors cell transformation and tumorigenesis leading to a marked increase of malignancy of neuroblastoma cells. Therefore, our results highlight a novel regulatory pathway of considerable interest linking APP processing with cell cycle regulation and DNA-surveillance systems, that may represent a molecular mechanism to induce neurodegeneration in post-mitotic neurons.

AB - FE65 proteins constitute a family of adaptors which modulates the processing of amyloid precursor protein and the consequent amyloid β production. Thus, they have been involved in the complex and partially unknown cascade of reactions at the base of Alzheimer's disease etiology. However, FE65 and FE65-like proteins may be linked to neurodegeneration through the regulation of cell cycle in post-mitotic neurons. In this work we disclose novel molecular mechanisms by which APBB2 can modulate APP processing. We show that APBB2 mRNA splicing, driven by the over-expression of a novel non-coding RNA named 45A, allow the generation of alternative protein forms endowed with differential effects on Aβ production, cell cycle control, and DNA damage response. 45A overexpression also favors cell transformation and tumorigenesis leading to a marked increase of malignancy of neuroblastoma cells. Therefore, our results highlight a novel regulatory pathway of considerable interest linking APP processing with cell cycle regulation and DNA-surveillance systems, that may represent a molecular mechanism to induce neurodegeneration in post-mitotic neurons.

KW - β amyloid

KW - APBB2 alternative splicing

KW - Cell cycle progression non-coding RNA

KW - Neurodegeneration

KW - RNA polymerase III

UR - http://www.scopus.com/inward/record.url?scp=84880008229&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880008229&partnerID=8YFLogxK

U2 - 10.1016/j.bbamcr.2013.02.020

DO - 10.1016/j.bbamcr.2013.02.020

M3 - Article

VL - 1833

SP - 1511

EP - 1526

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

SN - 0167-4889

IS - 6

ER -