Pre-mRNA splicing involves cutting out unneeded sequences and piecing the mRNAs together before they are exported from the nucleus and translated into proteins.
"That study gave us the clue that MALAT1 is an important gene that might be involved in pre-mRNA metabolism," Prasanth said.
In the new study, Prasanth and his colleagues tested the hypothesis that MALAT1 interacts with and modulates the behavior of a group of pre-mRNA splicing factors known as the SR-family splicing factors.
The researchers found that the MALAT1 sequence contains multiple regions that can bind SR-splicing proteins. Further experiments showed that MALAT1 does indeed bind to several members of the SR-proteins the team analyzed.
Furthermore, depleting cells of MALAT1 or over-expressing the splicing factors to which it can bind led to the same alteration in the splicing of a large number of pre-mRNAs in the cells, suggesting that MALAT1 latches onto the splicing factors and regulates their access to new transcripts.
"All of the data strongly suggest that MALAT1 is acting as a regulator of splicing by modulating the levels of the splicing factors in the cell," Prasanth said.
This study verifies that MALAT1 plays a key role in pre-mRNA processing, with broad implications for human health, Prasanth said.
"Numerous studies have shown that aberrant splicing of pre-mRNA is a major issue associated with several diseases, including cancer," he said. "Some of the factors we know interact with MALAT1 have been shown to be oncogenes. If you over-express these genes you can make a cell cancerous."
"Similarly, some of the genes whose pre-mRNA splicing is controlled by MALAT1 are members of the cancer 'signature genes,' " Prasanth said. "This means that
|Contact: Diana Yates|
University of Illinois at Urbana-Champaign