scholarly journals Son Is Essential for Nuclear Speckle Organization and Cell Cycle Progression

2010 ◽  
Vol 21 (4) ◽  
pp. 650-663 ◽  
Author(s):  
Alok Sharma ◽  
Hideaki Takata ◽  
Kei-ichi Shibahara ◽  
Athanasios Bubulya ◽  
Paula A. Bubulya

Subnuclear organization and spatiotemporal regulation of pre-mRNA processing factors is essential for the production of mature protein-coding mRNAs. We have discovered that a large protein called Son has a novel role in maintaining proper nuclear organization of pre-mRNA processing factors in nuclear speckles. The primary sequence of Son contains a concentrated region of multiple unique tandem repeat motifs that may support a role for Son as a scaffolding protein for RNA processing factors in nuclear speckles. We used RNA interference (RNAi) approaches and high-resolution microscopy techniques to study the functions of Son in the context of intact cells. Although Son precisely colocalizes with pre-mRNA splicing factors in nuclear speckles, its depletion by RNAi leads to cell cycle arrest in metaphase and causes dramatic disorganization of small nuclear ribonuclear protein and serine-arginine rich protein splicing factors during interphase. Here, we propose that Son is essential for appropriate subnuclear organization of pre-mRNA splicing factors and for promoting normal cell cycle progression.

Genetics ◽  
2000 ◽  
Vol 156 (4) ◽  
pp. 1503-1517 ◽  
Author(s):  
Sigal Ben-Yehuda ◽  
Ian Dix ◽  
Caroline S Russell ◽  
Margaret McGarvey ◽  
Jean D Beggs ◽  
...  

AbstractThe PRP17/CDC40 gene of Saccharomyces cerevisiae functions in two different cellular processes: pre-mRNA splicing and cell cycle progression. The Prp17/Cdc40 protein participates in the second step of the splicing reaction and, in addition, prp17/cdc40 mutant cells held at the restrictive temperature arrest in the G2 phase of the cell cycle. Here we describe the identification of nine genes that, when mutated, show synthetic lethality with the prp17/cdc40Δ allele. Six of these encode known splicing factors: Prp8p, Slu7p, Prp16p, Prp22p, Slt11p, and U2 snRNA. The other three, SYF1, SYF2, and SYF3, represent genes also involved in cell cycle progression and in pre-mRNA splicing. Syf1p and Syf3p are highly conserved proteins containing several copies of a repeated motif, which we term RTPR. This newly defined motif is shared by proteins involved in RNA processing and represents a subfamily of the known TPR (tetratricopeptide repeat) motif. Using two-hybrid interaction screens and biochemical analysis, we show that the SYF gene products interact with each other and with four other proteins: Isy1p, Cef1p, Prp22p, and Ntc20p. We discuss the role played by these proteins in splicing and cell cycle progression.


RNA ◽  
2000 ◽  
Vol 6 (11) ◽  
pp. 1565-1572 ◽  
Author(s):  
CAROLINE S. RUSSELL ◽  
SIGAL BEN-YEHUDA ◽  
IAN DIX ◽  
MARTIN KUPIEC ◽  
JEAN D. BEGGS

2003 ◽  
Vol 14 (3) ◽  
pp. 1043-1057 ◽  
Author(s):  
Kannanganattu V. Prasanth ◽  
Paula A. Sacco-Bubulya ◽  
Supriya G. Prasanth ◽  
David L. Spector

In eukaryotic cells, RNA polymerase II (RNA pol II) transcription and pre-mRNA processing are coordinated events. We have addressed how individual components of the transcription and pre-mRNA processing machinery are organized during mitosis and subsequently recruited into the newly formed daughter nuclei. Interestingly, localization studies of numerous RNA pol II transcription and pre-mRNA processing factors revealed a nonrandom and sequential entry of these factors into daughter nuclei after nuclear envelope/lamina formation. The initiation competent form of RNA pol II and general transcription factors appeared in the daughter nuclei simultaneously, but prior to pre-mRNA processing factors, whereas the elongation competent form of RNA pol II was detected even later. The differential entry of these factors rules out the possibility that they are transported as a unitary complex. Telophase nuclei were competent for transcription and pre-mRNA splicing concomitant with the initial entry of the respective factors. In addition, our results revealed a low turnover rate of transcription and pre-mRNA splicing factors during mitosis. We provide evidence to support a model in which the entry of the RNA pol II gene expression machinery into newly forming daughter nuclei is a staged and ordered process.


RNA ◽  
2021 ◽  
pp. rna.078935.121
Author(s):  
Elena Martin ◽  
Claudia Vivori ◽  
Malgorzata Rogalska ◽  
Jorge Herrero ◽  
Juan Valcarcel

The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140 and CHERP form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulate the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.


Yeast ◽  
2000 ◽  
Vol 16 (11) ◽  
pp. 1001-1013 ◽  
Author(s):  
Mitchell Beales ◽  
Nina Flay ◽  
Ron McKinney ◽  
Yasuaki Habara ◽  
Yasumi Ohshima ◽  
...  

2004 ◽  
Vol 279 (31) ◽  
pp. 32839-32847 ◽  
Author(s):  
Xiaojing Sun ◽  
Hua Zhang ◽  
Dan Wang ◽  
Dalong Ma ◽  
Yan Shen ◽  
...  

2016 ◽  
Vol 291 (53) ◽  
pp. 27387-27402 ◽  
Author(s):  
Nagampalli Vijaykrishna ◽  
Geetha Melangath ◽  
Rakesh Kumar ◽  
Piyush Khandelia ◽  
Pushpinder Bawa ◽  
...  

2012 ◽  
Vol 23 (18) ◽  
pp. 3694-3706 ◽  
Author(s):  
Vidisha Tripathi ◽  
David Y. Song ◽  
Xinying Zong ◽  
Sergey P. Shevtsov ◽  
Stephen Hearn ◽  
...  

The mammalian cell nucleus is compartmentalized into nonmembranous subnuclear domains that regulate key nuclear functions. Nuclear speckles are subnuclear domains that contain pre-mRNA processing factors and noncoding RNAs. Many of the nuclear speckle constituents work in concert to coordinate multiple steps of gene expression, including transcription, pre-mRNA processing and mRNA transport. The mechanism that regulates the formation and maintenance of nuclear speckles in the interphase nucleus is poorly understood. In the present study, we provide evidence for the involvement of nuclear speckle resident proteins and RNA components in the organization of nuclear speckles. SR-family splicing factors and their binding partner, long noncoding metastasis-associated lung adenocarcinoma transcript 1 RNA, can nucleate the assembly of nuclear speckles in the interphase nucleus. Depletion of SRSF1 in human cells compromises the association of splicing factors to nuclear speckles and influences the levels and activity of other SR proteins. Furthermore, on a stably integrated reporter gene locus, we demonstrate the role of SRSF1 in RNA polymerase II–mediated transcription. Our results suggest that SR proteins mediate the assembly of nuclear speckles and regulate gene expression by influencing both transcriptional and posttranscriptional activities within the cell nucleus.


2018 ◽  
Author(s):  
Jung-Sik Kim ◽  
Xiaoyuan He ◽  
Jie Liu ◽  
Zhijun Duan ◽  
Taeyeon Kim ◽  
...  

AbstractThe cohesin complex regulates sister chromatid cohesion, chromosome organization, gene expression, and DNA repair. Here we report that endogenous human cohesin interacts with a panoply of splicing factors and RNA binding proteins, including diverse components of the U4/U6.U5 tri-snRNP complex and several splicing factors that are commonly mutated in cancer. The interactions are enhanced during mitosis, and the interacting splicing factors and RNA binding proteins follow the cohesin cycle and prophase pathway of regulated interactions with chromatin. Depletion of cohesin-interacting splicing factors results in stereotyped cell cycle arrests and alterations in genomic organization. These data support the hypothesis that splicing factors and RNA binding proteins control cell cycle progression and genomic organization via regulated interactions with cohesin and chromatin.One Sentence SummaryEndogenous tagging reveals that cohesin interacts with diverse chromatin-bound splicing factors that regulate cell cycle progression and genomic organization in human cells.


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