scholarly journals RRP7A links primary microcephaly to dysfunction of ribosome biogenesis, resorption of primary cilia, and neurogenesis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Muhammad Farooq ◽  
Louise Lindbæk ◽  
Nicolai Krogh ◽  
Canan Doganli ◽  
Cecilie Keller ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Primary Cilia ◽  
Brain Size ◽  
Cell Model ◽  
Pathophysiological Mechanism ◽  
Primary Microcephaly ◽  
Ribosomal Rna Processing

AbstractPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

scholarly journals RRP7A links primary microcephaly to radial glial cells and dysfunction of ribosomal biogenesis, neurogenesis and ciliary resorption

2019 ◽  
Author(s):  
Muhammad Farooq ◽  
Louise Lindbæk ◽  
Nicolai Krogh ◽  
Canan Doganli ◽  
Cecilie Keller ◽  
...  
Keyword(s):  
Glial Cells ◽  
Ribosomal Rna ◽  
Rna Processing ◽  
Brain Size ◽  
Cell Model ◽  
Pathophysiological Mechanism ◽  
Primary Microcephaly ◽  
Radial Glial Cells ◽  
Ribosomal Rna Processing ◽  
Radial Glial

Introductory paragraphPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability1. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role1. Using homozygosity mapping and whole exome sequencing, we identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, which segregated with MCPH in a consanguineous family with 10 affected individuals. RRP7A is expressed in neural stem cells/radial glial cells of the developing human forebrain, and targeted mutation of Rrp7a leads to defects in both neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in processing of ribosomal RNA, resorption of primary cilia and cell cycle progression. Finally, analysis of zebrafish embryos with loss-of-function mutation in rrp7a confirmed that RRP7A depletion causes reduced brain size, impaired neurogenesis and cell proliferation as well as defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

Red/green Dual Fluorescence Detection of Both the Nucleus and Nucleolus in Living Cells

2009 ◽  
Vol 17 (4) ◽  
pp. 18-21 ◽  
Author(s):  
Jack Coleman ◽  
Hilary Cox ◽  
Zaiguo Li ◽  
Praveen Pande ◽  
Dee Shen ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Dna And Rna ◽  
Nuclear Domain ◽  
Immunodeficiency Virus ◽  
Ribosomal Rna Processing ◽  
Hiv 1

The nucleolus represents a highly dynamic nuclear domain arising from an equilibrium between the level of ribosomal RNA synthesis and the efficiency of ribosomal RNA processing [1, 2]. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now demonstrate that it has additional functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response, and biogenesis of multiple ribonucleoprotein particles. Ribosome biogenesis is regulated throughout interphase and ceases during mitosis (Figure 1). Thus, there is a direct relationship between cell growth and nucleolar activities. Nucleoli are well known to be dramatically modified in cancer cells. Additionally, a large number of key proteins from both DNA- and RNA-containing viruses are localized in the nucleolus, including the human immunodeficiency virus (HIV)-1 Rev and Tat proteins. Targeting of viral proteins to the nucleolus not only facilitates virus replication, but may also be required for pathogenic processes. The nucleolus can also be considered a sensor of stress due to the redistribution of the ribosomal proteins in the nucleoplasm through its disruption.

Adenovirus infection retards ribosomal RNA processing

1989 ◽  
Vol 138 (1) ◽  
pp. 205-207 ◽  
Author(s):  
Susan H. Lawler ◽  
Robert W. Jones ◽  
Brian P. Eliceiri ◽  
George L. Eliceiri
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Adenovirus Infection ◽  
Ribosomal Rna Processing

Developmental expression of fibrillarin and U3 snRNA in Xenopus laevis

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 317-326
Author(s):  
M. Caizergues-Ferrer ◽  
C. Mathieu ◽  
P. Mariottini ◽  
F. Amalric ◽  
F. Amaldi
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Protein Detection ◽  
Developmental Expression ◽  
Oocyte Growth ◽  
Small Nuclear Ribonucleoprotein ◽  
Hybridization Probes ◽  
Ribosomal Rna Processing ◽  
Protein Components ◽  
Nuclear Ribonucleoprotein

Fibrillarin is one of the protein components that together with U3 snRNA constitute the U3 snRNP, a small nuclear ribonucleoprotein particle involved in ribosomal RNA processing in eucaryotic cells. Using an antifibrillarin antiserum for protein detection and a fibrillarin cDNA and a synthetic oligonucleotide complementary to U3 snRNA as hybridization probes, the expression of these two components has been studied during Xenopus development. Fibrillarin mRNA is accumulated early in oogenesis, like many other messengers, and translated during oocyte growth. Fibrillarin protein is thus progressively accumulated throughout oogenesis to be assembled with U3 snRNA and used for ribosome production in the amplified nucleoli. After fertilization, the amount of U3 snRNA decreases while the maternally accumulated fibrillarin mRNA is maintained and utilized to produce more protein. After the mid-blastula transition, stored fibrillarin is assembled with newly synthesized U3 snRNA and becomes localized in the prenucleolar bodies and reforming nucleoli.

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