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Masatoshi Mutazono, Misato Morita, Chihiro Tsukahara, Madoka Chinen, Shiori Nishioka, Tatsuhiro Yumikake, Kohei Dohke, Misuzu Sakamoto, Takashi Ideue, Jun-ichi Nakayama, Kojiro Ishii, Tokio Tani
The intron in centromeric noncoding RNA facilitates RNAi-mediated formation of heterochromatin
www.plosgenetics.org
www.plosgenetics.org
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0.652 0 Td
[()11()-20()]TJ
/F8 1 Tf
2.4604 0 Td
(allele.)Tj
2.4661 0 Td
(Hereafter,)Tj
4.2463 0 Td
(we)Tj
1.3266 0 Td
(refer)Tj
2.0976 0 Td
(to)Tj
/F9 1 Tf
1.0262 0 Td
[()11()-20()]TJ
/F8 1 Tf
2.4604 0 Td
(and)Tj
1.7347 0 Td
(its)Tj
1.1452 0 Td
(wild-type)Tj
3.9912 0 Td
(product)Tj
3.3902 0 Td
(as)Tj
/F9 1 Tf
-35.6992 -1.2983 Td
[()11()-20()]TJ
/F8 1 Tf
2.4604 0 Td
(and)Tj
1.7292 0 Td
(spPrp16p,)Tj
4.2406 0 Td
(respectively.)Tj
-7.234 -1.3039 Td
(S)Tj
-0.01 Tc
(ome)Tj
2.4321 0 Td
(splicing)Tj
3.2655 0 Td
(mutants)Tj
3.4639 0 Td
(are)Tj
1.4343 0 Td
(defective)Tj
3.6964 0 Td
(in)Tj
1.0205 0 Td
(the)Tj
1.4513 0 Td
(RNAi-mediated)Tj
6.5253 0 Td
(formation)Tj
4.2065 0 Td
(of)Tj
1.0035 0 Td
(centromeric)Tj
5.0342 0 Td
(hetero-)Tj
-34.7297 -1.2982 Td
(chromatin)Tj
4.3596 0 Td
(in)Tj
/F9 1 Tf
1.0262 0 Td
[()]TJ
/F8 1 Tf
(.)Tj
/F9 1 Tf
0.8901 0 Td
[()4()11()17()4()]TJ
/F8 1 Tf
2.7722 0 Td
([)Tj
0.83 0.64 0.02 0 k
(5)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2473 0 Td
(6)Tj
0 g
(],)Tj
1.2415 0 Td
(and)Tj
1.7121 0 Td
(we)Tj
1.3153 0 Td
(proposed)Tj
3.9061 0 Td
(a)Tj
0.6463 0 Td
(model)Tj
2.7156 0 Td
(in)Tj
1.0205 0 Td
(which)Tj
2.6248 0 Td
(the)Tj
1.4513 0 Td
(spliceosome)Tj
5.0059 0 Td
(or)Tj
1.0885 0 Td
(sub-spli-)Tj
-33.0233 -1.2983 Td
(ceosome)Tj
3.6397 0 Td
(forms)Tj
2.5398 0 Td
(a)Tj
0.6463 0 Td
(platform)Tj
3.6566 0 Td
(for)Tj
1.3663 0 Td
(the)Tj
1.4514 0 Td
(recruitment)Tj
4.9265 0 Td
(of)Tj
1.0035 0 Td
(RNAi)Tj
2.5058 0 Td
(factors)Tj
2.863 0 Td
(to)Tj
1.0091 0 Td
(ncRNAs)Tj
3.5602 0 Td
(transcribed)Tj
4.6885 0 Td
(from)Tj
2.1826 0 Td
(the)Tj
-36.0393 -1.2983 Td
(centromere)Tj
4.7678 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
1.5761 0 Td
(We)Tj
1.5987 0 Td
(found)Tj
2.5909 0 Td
(that)Tj
/F9 1 Tf
1.7518 0 Td
[()11()-20()]TJ
/F8 1 Tf
3.2201 0 Td
(was)Tj
1.6781 0 Td
(hypersensitive)Tj
5.8337 0 Td
(to)Tj
1.0148 0 Td
(the)Tj
1.4513 0 Td
(microtubule-destabilizin)Tj
9.6887 0 Td
(g)Tj
-35.172 -1.3039 Td
(drug)Tj
2.0863 0 Td
(thiabendazole)Tj
5.6976 0 Td
(\(TBZ\))Tj
2.6645 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.7972 0 Td
(1A)Tj
0 g
(\))Tj
1.7008 0 Td
(and)Tj
1.7121 0 Td
(accumulated)Tj
5.2384 0 Td
(unprocessed)Tj
/F9 1 Tf
5.1476 0 Td
[()10()]TJ
/F8 1 Tf
1.1168 0 Td
(ncRNA)Tj
3.2031 0 Td
(transcribed)Tj
4.6885 0 Td
(from)Tj
-35.0529 -1.2983 Td
(centromeres)Tj
5.125 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(],)Tj
1.576 0 Td
(suggesting)Tj
4.3427 0 Td
(that)Tj
/F9 1 Tf
1.7575 0 Td
[()11()-20()]TJ
/F8 1 Tf
2.4321 0 Td
(has)Tj
1.525 0 Td
(defects)Tj
2.9197 0 Td
(in)Tj
1.0261 0 Td
(the)Tj
1.4513 0 Td
(attachment)Tj
4.6657 0 Td
(of)Tj
1.0035 0 Td
(microtubules)Tj
5.4255 0 Td
(to)Tj
1.0148 0 Td
(kineto-)Tj
-34.2649 -1.2982 Td
(chores)Tj
2.7949 0 Td
(and)Tj
1.7121 0 Td
(formation)Tj
4.2066 0 Td
(of)Tj
1.0035 0 Td
(centromeric)Tj
5.0343 0 Td
(heterochromatin.)Tj
-0.004 Tc
-13.5552 -1.3039 Td
(We)Tj
1.6101 0 Td
(further)Tj
3.0274 0 Td
(characterized)Tj
/F9 1 Tf
5.5615 0 Td
[()11()-20()]TJ
/F8 1 Tf
2.4605 0 Td
(in)Tj
1.0374 0 Td
(terms)Tj
2.4945 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(relationship)Tj
4.989 0 Td
(between)Tj
3.5262 0 Td
(the)Tj
1.474 0 Td
(splicing)Tj
3.3165 0 Td
(machinery)Tj
-33.1764 -1.2983 Td
(and)Tj
1.7291 0 Td
(centromeric)Tj
5.0967 0 Td
(gene)Tj
2.0806 0 Td
(silencing.)Tj
3.9968 0 Td
(As)Tj
1.2643 0 Td
(shown)Tj
2.8516 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0318 0 Td
(Fig)Tj
1.4797 0 Td
(1B)Tj
0 g
(,)Tj
1.5023 0 Td
(the)Tj
/F9 1 Tf
1.4684 0 Td
[()11()-20()]TJ
/F8 1 Tf
3.2598 0 Td
(mutant)Tj
3.1463 0 Td
(exhibited)Tj
3.9288 0 Td
(a)Tj
0.652 0 Td
(high)Tj
2.0069 0 Td
(inci-)Tj
-35.4951 -1.2983 Td
(dence)Tj
2.5682 0 Td
(of)Tj
1.0148 0 Td
(lagging)Tj
3.1067 0 Td
(chromosomes)Tj
5.8507 0 Td
(during)Tj
2.9253 0 Td
(mitosis,)Tj
3.3279 0 Td
(consistent)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(defective)Tj
3.7529 0 Td
(attachment)Tj
4.7225 0 Td
(of)Tj
1.0148 0 Td
(micro-)Tj
-34.537 -1.3039 Td
(tubules)Tj
3.1124 0 Td
(to)Tj
1.0205 0 Td
(kinetochores.)Tj
5.6012 0 Td
(To)Tj
1.3379 0 Td
(examine)Tj
3.6057 0 Td
(the)Tj
1.4683 0 Td
(integrity)Tj
3.6113 0 Td
(of)Tj
1.0148 0 Td
(pericentromeric)Tj
6.6783 0 Td
(heterochromatin,)Tj
7.1943 0 Td
(which)Tj
-34.6447 -1.2982 Td
(is)Tj
0.8447 0 Td
(required)Tj
3.6397 0 Td
(for)Tj
1.3889 0 Td
(the)Tj
1.4684 0 Td
(proper)Tj
2.9253 0 Td
(assembly)Tj
3.8268 0 Td
(of)Tj
1.0148 0 Td
(kinetochores,)Tj
5.6012 0 Td
(we)Tj
1.3266 0 Td
(constructed)Tj
/F9 1 Tf
4.9321 0 Td
[()11()-20()]TJ
/F8 1 Tf
3.2599 0 Td
(with)Tj
1.9955 0 Td
(the)Tj
/F9 1 Tf
1.4684 0 Td
[()12()20(\n)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 555.3637 390.6708 cm
BT
/F9 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 373.2094 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(marker)Tj
3.135 0 Td
(gene)Tj
2.0807 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
/F9 1 Tf
1.4684 0 Td
[()12()7()]TJ
/F8 1 Tf
1.8085 0 Td
(region)Tj
2.8006 0 Td
(of)Tj
1.0204 0 Td
(centromere)Tj
4.8303 0 Td
(1)Tj
0.6916 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(S2)Tj
1.5137 0 Td
(Fig)Tj
0 g
(\),)Tj
2.0466 0 Td
(and)Tj
1.7291 0 Td
(then)Tj
2.0183 0 Td
(serially)Tj
3.0217 0 Td
(spotted)Tj
3.1521 0 Td
(the)Tj
1.474 0 Td
(resultant)Tj
-33.8284 -1.2982 Td
(cells)Tj
1.9218 0 Td
(onto)Tj
2.0806 0 Td
(plates)Tj
2.5002 0 Td
(with)Tj
1.9956 0 Td
(or)Tj
1.0998 0 Td
(without)Tj
3.3279 0 Td
(5-fluoroorotic)Tj
5.8676 0 Td
(acid)Tj
1.8709 0 Td
(\(5-FOA\).)Tj
3.9118 0 Td
(As)Tj
1.2642 0 Td
(shown)Tj
2.846 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0375 0 Td
(Fig)Tj
1.4796 0 Td
(2A)Tj
0 g
(,)Tj
/F9 1 Tf
1.6044 0 Td
[()11()-20()]TJ
/F8 1 Tf
-32.8079 -1.3039 Td
(cells)Tj
1.9218 0 Td
(harboring)Tj
4.218 0 Td
(the)Tj
1.4683 0 Td
(inserted)Tj
/F9 1 Tf
3.4412 0 Td
[()12()20(\n)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 328.8755 351.6661 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(+)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 335.4519 347.1874 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(gene)Tj
2.0806 0 Td
(were)Tj
2.1203 0 Td
(highly)Tj
2.7099 0 Td
(sensitive)Tj
3.6226 0 Td
(to)Tj
1.0262 0 Td
(5-FOA,)Tj
3.2314 0 Td
(similar)Tj
2.9877 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
/F9 1 Tf
1.4683 0 Td
[( )7()-13()]TJ
/F8 1 Tf
1.9446 0 Td
(het-)Tj
-35.7616 -1.2982 Td
(erochromatin)Tj
5.7203 0 Td
(protein)Tj
3.1521 0 Td
(mutant,)Tj
3.3732 0 Td
(suggesting)Tj
4.3992 0 Td
(that,)Tj
2.0069 0 Td
(in)Tj
1.0319 0 Td
(these)Tj
2.2563 0 Td
(mutants,)Tj
3.7304 0 Td
(the)Tj
/F9 1 Tf
1.474 0 Td
[()12()20(\n)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 489.8267 338.6267 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(+)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 496.3464 334.2047 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(gene)Tj
2.0806 0 Td
(was)Tj
1.7007 0 Td
(expressed)Tj
-33.4144 -1.2982 Td
(when)Tj
2.4037 0 Td
(inserted)Tj
3.4413 0 Td
(in)Tj
1.0318 0 Td
(centromeric)Tj
5.1023 0 Td
(regions.)Tj
3.3845 0 Td
(By)Tj
1.2586 0 Td
(contrast,)Tj
3.685 0 Td
(a)Tj
0.652 0 Td
(wild-type)Tj
3.9911 0 Td
(strain)Tj
2.5002 0 Td
(harboring)Tj
4.2178 0 Td
(the)Tj
/F9 1 Tf
1.474 0 Td
[()12()20(\n)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 549.8078 325.644 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(+)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 556.3842 321.222 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(gene)Tj
-35.6369 -1.3039 Td
(inserted)Tj
3.4412 0 Td
(into)Tj
1.8369 0 Td
(the)Tj
/F9 1 Tf
1.474 0 Td
[()12()7()]TJ
/F8 1 Tf
1.8085 0 Td
(region)Tj
2.8006 0 Td
(grew)Tj
2.1657 0 Td
(well)Tj
1.8198 0 Td
(on)Tj
1.2756 0 Td
(5-FOA)Tj
3.0047 0 Td
(plates.)Tj
2.7269 0 Td
(RT-PCR)Tj
3.6453 0 Td
(analysis)Tj
3.3279 0 Td
(also)Tj
1.7688 0 Td
(revealed)Tj
3.5206 0 Td
(that)Tj
-34.6165 -1.2982 Td
(the)Tj
/F9 1 Tf
1.4683 0 Td
[()12()20(\n)]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 233.1212 299.622 cm
BT
/F8 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(+)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 239.6409 295.2 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(gene)Tj
2.0806 0 Td
(inserted)Tj
3.4412 0 Td
(into)Tj
1.8425 0 Td
(the)Tj
/F9 1 Tf
1.4684 0 Td
[()12()7()]TJ
/F8 1 Tf
1.8084 0 Td
(region)Tj
2.8007 0 Td
(was)Tj
1.7007 0 Td
(expressed)Tj
4.0932 0 Td
(as)Tj
1.0148 0 Td
(in)Tj
1.0375 0 Td
(a)Tj
/F9 1 Tf
0.652 0 Td
[( )7()-13()]TJ
/F8 1 Tf
1.9445 0 Td
(mutant)Tj
3.1465 0 Td
(harboring)Tj
4.2236 0 Td
(the)Tj
-35.2174 -1.2982 Td
(same)Tj
2.2564 0 Td
(insertion)Tj
3.8153 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
1.8198 0 Td
(2B)Tj
0 g
(\).)Tj
-6.6952 -1.3039 Td
(T)Tj
-0.014 Tc
(o)Tj
1.3322 0 Td
(further)Tj
2.9536 0 Td
(demonstrate)Tj
5.125 0 Td
(the)Tj
1.44 0 Td
(impaired)Tj
3.7701 0 Td
(formation)Tj
4.1669 0 Td
(of)Tj
0.9978 0 Td
(centromeric)Tj
4.9889 0 Td
(heterochromatin)Tj
6.8144 0 Td
(in)Tj
/F9 1 Tf
1.0205 0 Td
[()11()-20()]TJ
/F8 1 Tf
(,)Tj
2.6249 0 Td
(we)Tj
-36.4306 -1.2983 Td
(performed)Tj
4.3766 0 Td
(a)Tj
0.635 0 Td
(chromatin)Tj
4.3256 0 Td
(immunoprecipitation)Tj
8.657 0 Td
(\(ChIP\))Tj
2.9253 0 Td
(analysis)Tj
3.2428 0 Td
(using)Tj
2.3357 0 Td
(an)Tj
1.1792 0 Td
(anti-H3K9)Tj
4.4164 0 Td
(dimethylation)Tj
-32.0936 -1.2983 Td
(\(H3K9me2\))Tj
4.9209 0 Td
(antibody.)Tj
3.9004 0 Td
(As)Tj
1.2416 0 Td
(shown)Tj
2.8006 0 Td
(in)Tj
0.83 0.64 0.02 0 k
1.0148 0 Td
(Fig)Tj
1.4513 0 Td
(2C)Tj
0 g
(,)Tj
1.5534 0 Td
(the)Tj
/F9 1 Tf
1.44 0 Td
[()11()-20()]TJ
/F8 1 Tf
2.4151 0 Td
(mutation)Tj
3.8381 0 Td
(decreased)Tj
4.0478 0 Td
(the)Tj
1.44 0 Td
(H3K9me2)Tj
4.2576 0 Td
(level)Tj
1.9672 0 Td
(in)Tj
-36.2888 -1.3039 Td
(the)Tj
1.44 0 Td
(pericentromeric)Tj
6.5252 0 Td
(region)Tj
2.744 0 Td
(to)Tj
1.0034 0 Td
(a)Tj
0.6463 0 Td
(level)Tj
1.9616 0 Td
(observed)Tj
3.719 0 Td
(in)Tj
/F13 1 Tf
1.0148 0 Td
( )Tj
/F9 1 Tf
[()4()1()]TJ
/F8 1 Tf
(,)Tj
2.6702 0 Td
(indicating)Tj
4.1669 0 Td
(defective)Tj
3.6567 0 Td
(formation)Tj
4.1726 0 Td
(of)Tj
0.9978 0 Td
(peri-)Tj
-34.7185 -1.2982 Td
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4.9889 0 Td
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6.8144 0 Td
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1.0148 0 Td
[()11()-20()]TJ
/F8 1 Tf
(.)Tj
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1.0885 0 Td
(addition,)Tj
3.736 0 Td
(northern)Tj
3.736 0 Td
(blot)Tj
1.7348 0 Td
(analysis)Tj
3.2485 0 Td
(revealed)Tj
3.4469 0 Td
(that)Tj
1.7348 0 Td
(the)Tj
-34.1742 -1.2983 Td
(amount)Tj
3.2939 0 Td
(of)Tj
0.9977 0 Td
(centromeric)Tj
4.9832 0 Td
(siRNAs)Tj
3.1918 0 Td
(derived)Tj
3.1465 0 Td
(from)Tj
/F9 1 Tf
2.1656 0 Td
[()10()]TJ
/F8 1 Tf
1.1112 0 Td
(ncRNA)Tj
3.1805 0 Td
(was)Tj
1.6724 0 Td
(markedly)Tj
3.9118 0 Td
(reduced)Tj
3.3788 0 Td
(in)Tj
/F9 1 Tf
1.0148 0 Td
[()11()-20()]TJ
/F8 1 Tf
3.1862 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Fig)Tj
-35.2344 -1.2983 Td
(2D)Tj
0 g
(,)Tj
1.6271 0 Td
(lane)Tj
1.8312 0 Td
(5\),)Tj
1.2301 0 Td
(consistent)Tj
4.1556 0 Td
(with)Tj
1.9615 0 Td
(our)Tj
1.5931 0 Td
(previous)Tj
3.5716 0 Td
(report)Tj
2.6476 0 Td
(showing)Tj
3.5092 0 Td
(that)Tj
/F9 1 Tf
1.7405 0 Td
[()11()-20()]TJ
/F8 1 Tf
2.4151 0 Td
(accumulates)Tj
5.0286 0 Td
(unprocessed)Tj
/F9 1 Tf
5.1024 0 Td
[()10()]TJ
/F8 1 Tf
-36.4136 -1.3039 Td
(ncRNA)Tj
3.1805 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(].)Tj
1.5646 0 Td
(These)Tj
2.5172 0 Td
(results)Tj
2.7382 0 Td
(suggested)Tj
3.9855 0 Td
(that)Tj
1.7348 0 Td
(processing)Tj
4.3653 0 Td
(of)Tj
0.9978 0 Td
(centromeric)Tj
4.9889 0 Td
(ncRNAs)Tj
3.532 0 Td
(is)Tj
0.8277 0 Td
(defective)Tj
3.6623 0 Td
(in)Tj
/F9 1 Tf
1.0148 0 Td
[()11()-20()]TJ
/F8 1 Tf
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