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Assembly o he nucleolus: in need
o e ision
Ma ia Ca mo-Fonseca
Ou cu en iew o he nucleolus has
been shaped by he concep ha he o ga-
niza ion o his p ominen compa men
wi hin he nucleus is p ima ily dic a ed by
i s unc ion, he making o ibosome sub-
uni s. Whe he ibosome biogenesis is
amed by a dedica ed nucleola sca old
has emained unclea . In his issue o The
EMBO Jou nal, Caud on-He ge and collea-
gues p esen e idence o a nucleola
skele on composed o non-coding RNA
en iched in Alu epea elemen s.
See also: M Caud on-He ge e al
(No embe 2015)
P oduc ion o ibosomes is i al o
li e, and euka yo ic cells e ol ed a
specialized compa men , he nucleo-
lus, whe e ibosomal RNA genes a e an-
sc ibed, p e- ibosomal RNA is p ocessed, and
p e- ibosomes a e assembled (Pede son,
2010). Mammalian cells ypically con ain a
ew nucleoli ha disappea du ing mi osis and
o m de no o in ea ly G1 a ound ibosomal
genes ( DNA). In humans, long s e ches o
DNA a ays loca ed on i e dis inc ch omo-
somes coalesce o o m be ween one and
h ee nucleoli (Sa ino e al, 2001). The DNA
ansc ip ion uni s coupled wi h binding si es
o he HMG-box p o ein UBF a e su icien o
di ec o ma ion o a nucleolus (G ob e al,
2013). Howe e , wha d i es he clus e ing o
DNA ansc ip ion uni s in o only one o a
ew nucleoli pe nucleus emains elusi e. The
new s udy by Caud on-He ge and colleagues
iden i ies non-coding RNAs en iched in Alu
epea elemen s as po en ially in ol ed in his
p ocess.
The e a e o e 1 million copies o Alu
elemen s in he human genome, many o
which localize wi hin in ons o p o ein-
coding genes (Deininge , 2011). Acco ding
o Caud on-He ge e al (2015), s able sho
in on-de i ed RNAs con aining Alu epea
elemen s accumula e in he nucleolus and
a e essen ial o i s in eg i y. In he absence
o so-called aluRNAs, nucleoli dispe sed in o
smalle domains and DNA ansc ip ion
was se e ely educed. Nascen in onic Alu
RNAs we e p e iously shown o escape
deg ada ion a e p e-mRNA splicing, being
p ocessed and packaged in o me abolically
s able small ibonucleop o ein pa icles
(Ja
´dy e al, 2012). Howe e , hese p e i-
ously desc ibed RNA species we e exclu-
si ely de ec ed in he nucleoplasm (Ja
´dy
e al, 2012).
Caud on-He ge e al (2015) also ca ied
ou RNA e he ing expe imen s using a lacO
a ay consis ing o mul iple copies o he
NOR
NUCLEOLUS
UBF
NOR
aluRNA
Nucleolin/
Nucleophosmin
Exon In onic
Alu elemen
Exon
Figu e 1. Scheme illus a ing he aluRNA-sca old model.
Splicing o p e-mRNAs con aining in onic Alu elemen s gene a es sho aluRNAs ha associa e wi h nucleola
p o eins nucleolin and nucleophosmin. These aluRNAs, which a e capable o a ac ing genomic loci o he
nucleolus, c ea e a sca old ha may con ibu e o clus e ing o nucleola o ganizing egions (NORs) om
di e en ch omosomes ia in e ac ions wi h UBF.
Ins i u o de Medicina Molecula , Faculdade de Medicina, Uni e sidade de Lisboa, Lisboa, Po ugal. E-mail: ca mo[email p o ec ed]
DOI 10.15252/embj.201593185 | Published online 15 Oc obe 2015
ª2015 The Au ho The EMBO Jou nal Vol 34 |No22 |2015 2731
binding sequence o he lac ep esso
p o ein, LacI (She so & Dund , 2011).
AluRNA was agged wi h MS2 s em loops
and immobilized a he lacO a ay h ough
binding o MS2 p o ein used o LacI. This
esul ed in ec ui men o he lacO genomic
locus o he nucleolus. Nucleolin and nucleo-
phosmin, wo abundan s uc u al p o eins
o he nucleolus, we e u he shown o
in e ac in i o wi h aluRNAs. Based on
hese obse a ions, he ollowing model was
p oposed: (i) p e-mRNA splicing o p o ein-
coding genes con aining in onic Alu epea
elemen s gene a es small RNA species
e med aluRNAs; (ii) hese RNAs ac as a
sca old ha ec ui s nucleolin and nucleo-
phosmin; and (iii) in e ac ions be ween
nucleolin, nucleophosmin, and UBF esul in
coalescence o DNA a ays ha would
o he wise dispe se h oughou he nucleus
(Fig 1).
A ema kable ea u e o his model is ha
i explains he long-deba ed conund um ha
speci ic inhibi ion o RNA polyme ase II
(Pol II) causes disin eg a ion o nucleoli,
al hough e y li le Pol II ac i i y is de ec ed
in his nuclea compa men . Ine i ably,
howe e , his new model aises a numbe o
open ques ions. Fo example, Alu elemen s
a e p ima e speci ic, and al hough a ge ed
dis up ion o Alu- ela ed B1-con aining
RNAs causes nucleola dispe sion in mouse
cells (Caud on-He ge e al, 2015), i is
in iguing how dis inc RNA species co-
e ol ed a common nucleola sca olding
ole. I is also puzzling ha a subse o
in on-encoded Alu RNAs gene a e nucleo-
plasmic box H/ACA RNPs (Ja
´dy e al, 2012),
while o he s a e essen ial o nucleola o ga-
niza ion. Addi ional mechanis ic issues
conce n speci ici y o he in e ac ion
be ween nucleola aluRNAs and he e y
abundan nuclea p o eins nucleolin and
nucleophosmin. A inal emaining enigma is
how nucleola aluRNAs a e unc ionally
coupled o Pol I ac i i y. Clea ly, he
aluRNA-sca old model pa es he way o
u he esea ch ha will likely expand ou
unde s anding o how ibosome biogenesis
is con olled by nucleola biology.
Re e ences
Caud on-He ge M, Panke T, Seile J, Néme h A,
Voi R, G umm I, Rippe K (2015)Alu elemen -
con aining RNAs main ain nucleola s uc u e
and unc ion. EMBO J 34:2758 –2774
Deininge P (2011)Alu elemen s: know he SINES.
Genome Biol 12:236
G ob A, Colle an C, MacS ay B (2013) Cons uc ion
o syn he ic nucleoli in human cells e eals
how a majo unc ional nuclea domain is
o med and p opaga ed h ough cell di ision.
Genes De 28:220 –230
Jády B, Ke ele A, Kiss T (2012) Human in on-
encoded Alu RNAs a e p ocessed and packaged
in o Wd 79-associa ed nucleoplasmic box H/
ACA RNPs. Genes De 26:1897 –1910
Pede son T (2010) The Nucleolus. Cold Sp ing Ha b
Pe spec Biol 3:1
Sa ino TM, Geb ane-Younes J, De Mey J, Siba i a
JB, He nandez-Ve dun D (2001) Nucleola
assembly o he RNA p ocessing machine y in
li ing cells. J Cell Biol 153:1097 –1110
She so SP, Dund M (2011) Nuclea ion o
nuclea bodies by RNA. Na Cell Biol 13:
167 –173
The EMBO Jou nal Vol 34 |No22 |2015 ª2015 The Au ho
The EMBO Jou nal Assembly o he nucleolus: in need o e ision Ma ia Ca mo-Fonseca
2732