It is widely accepted that pre-mRNA maturation, including splicing, is tightly coupled to both transcription and mRNA export, but factors linking the three processes are less understood. By analysing the estrogen-regulated expression of the c-fos mRNA that is processed during transcription, we show that the ddx5 RNA helicase, is required throughout the major nuclear steps of the expression of t...

In article number 2000307, Tim Blomeier and co-workers describe the Blue Light-Operated CRISPR/Cas13b-mediated mRNA Knockdown. “Lockdown” introduces optical control of RNA levels utilizing a blue light-dependent switch to induce expression CRISPR/Cas13b, which mediates sequence-specific knockdown exo- endogenous mRNA. Further, they combined tool with other optogenetic switches for efficient dow...

Recent studies have shown that the putative RNA helicase protein UAP56 and its yeast homologue Sub2p are not only involved in pre-mRNA splicing but also required for the export of mRNA out of the nucleus, even if the mRNA is encoded by an intron-less gene.

The mRNA nuclear export receptor Mex67/Mtr2 is recruited to mRNAs through RNA-binding adaptors, including components of the THO/TREX complex that couple transcription to mRNA export. Here we show that the ubiquitin-associated (UBA) domain of Mex67 is not only required for proper nuclear export of mRNA but also contributes to recruitment of Mex67 to transcribing genes. Our results reveal that th...

Hypertrophic cardiomyopathy (HCM), characterized by asymmetric left ventricular hypertrophy, can lead to severe arrhythmias and sudden cardiac death. The mechanism underlying hypertrophy in HCM has not been fully elucidated. We recently showed that the messenger RNA (mRNA) transcriptome derived from myectomy tissue is gene expression reprogramming predominant transcriptional down-regulation of ...

In this paper we develop a model of stochastic gene expression, which is an extension of the model investigated in the paper [T. Lipniacki, P. Paszek, A. Marciniak-Czochra, A.R. Brasier, M. Kimmel, Transcriptional stochasticity in gene expression, J. Theor. Biol. 238 (2006) 348-367]. In our model, stochastic effects still originate from random fluctuations in gene activity status, but we preced...

Recent advances have led to a new understanding of how mRNAs are exported from the nucleus to the cytoplasm. This process requires a heterodimeric mRNA export receptor that is part of an elaborate machinery conserved from yeast to humans. Export of mRNAs is coupled to upstream steps in gene expression, such as pre-mRNA splicing, and to downstream events, including nonsense-mediated decay.

Fragile X syndrome is caused by the inactivation of the X-linked FMR1 gene, leading to the loss of its encoded protein FMRP. Although macroorchidism and defects in neuronal architecture and function have been associated with lack of FMRP, the exact molecular mechanism underlying this disease remains unclear. We have reported previously that in the brain and testis of mice, FMRP specifically int...

Autoregulatory loops often provide precise control of the level of expression of specific genes that encode key regulatory proteins. Here we have defined a pathway by which Yra1p, a yeast mRNA export factor, controls its own expression. We show that YRA1 exon 1 sequences in cis and Yra1p in trans inhibit YRA1 pre-mRNA splicing and commit the pre-mRNA to nuclear export. Mex67p and Crm1p jointly ...

Pre-mRNA splicing has to be coordinated with other processes occurring in the nucleus including transcription, mRNA 3' end formation and mRNA export. To analyze the relationship between transcription and splicing, we constructed a network of nested introns. Introns were inserted in the 5' splice site and/or branchpoint of a synthetic yeast intron interrupting a reporter gene. The inserted intro...