RESEARCH HIGHLIGHTS
A LT E R N AT I V E S P L I C I N G
This study identifies PRPF6 as an important driver of colon cancer cell growth
Alterations in components of the mRNA splicing machinery have been associated with cancer, but how these alterations affect tumorigenesis is unclear. Adler et al. found that the overexpression or amplification of pre-mRNA processing factor 6 (PRPF6) — a component of the trismall ribonucleoprotein (tri-snRNP) spliceosome complex — commonly occurs in human primary and metastatic colon cancer samples and may therefore be a driver of colon tumorigenesis. The authors found that knockdown of PRPF6 expression in human colon cancer cell lines expressing increased levels of PRPF6 inhibited their growth in vitro, and xenograft tumours derived from these PRPF6‑overexpressing cells underwent regression in vivo when PRPF6 was inducibly knocked down. Is spliceosome activity required for PRPF6‑induced growth? The expression of PRPF6 mutants that are
unable to coordinate splicing did not rescue the reduced growth phenotype in cells in which wild-type PRPF6 was knocked down, indicating that the splicing activity of PRPF6 is important for colon cancer cell growth. However, cell lines with highly expressed PRPF6 are not more susceptible to splicing impairment in general, as knockdown or inhibition of other spliceosome components did not reduce the growth of these cell lines. What splicing events are sensitive to PRPF6 loss? The authors found 25 gene isoforms that were down regulated on PRPF6 knockdown. In particular, expression of the splice variant of ZAK kinase, ZAK-LF, correlated with PRPF6 levels in colon cancer cells, and further experiments
NATURE REVIEWS | CANCER
NPG
Aberrant splicing promotes colon tumour growth
revealed that PRPF6 is required for alternative splicing of ZAK. Moreover, they showed that the expression of ZAK-LF transformed immortalized mouse fibroblasts and ZAK-LF knockdown reduced the growth of PRPF6‑overexpressing colon cancer cells in vitro and in xenografts. This study identifies PRPF6 as an important driver of colon cancer cell growth and suggests it promotes proliferation by preferential splicing of growth-promoting genes. Isabel Lokody ORIGINAL RESEARCH PAPER Adler, A. S. et al. An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth. Genes Dev. http://dx.doi.org/10.1101/ gad.237206.113 (2014)
VOLUME 14 | JUNE 2014 © 2014 Macmillan Publishers Limited. All rights reserved
A LT E R N AT I V E S P L I C I N G
This study identifies PRPF6 as an important driver of colon cancer cell growth
Alterations in components of the mRNA splicing machinery have been associated with cancer, but how these alterations affect tumorigenesis is unclear. Adler et al. found that the overexpression or amplification of pre-mRNA processing factor 6 (PRPF6) — a component of the trismall ribonucleoprotein (tri-snRNP) spliceosome complex — commonly occurs in human primary and metastatic colon cancer samples and may therefore be a driver of colon tumorigenesis. The authors found that knockdown of PRPF6 expression in human colon cancer cell lines expressing increased levels of PRPF6 inhibited their growth in vitro, and xenograft tumours derived from these PRPF6‑overexpressing cells underwent regression in vivo when PRPF6 was inducibly knocked down. Is spliceosome activity required for PRPF6‑induced growth? The expression of PRPF6 mutants that are
unable to coordinate splicing did not rescue the reduced growth phenotype in cells in which wild-type PRPF6 was knocked down, indicating that the splicing activity of PRPF6 is important for colon cancer cell growth. However, cell lines with highly expressed PRPF6 are not more susceptible to splicing impairment in general, as knockdown or inhibition of other spliceosome components did not reduce the growth of these cell lines. What splicing events are sensitive to PRPF6 loss? The authors found 25 gene isoforms that were down regulated on PRPF6 knockdown. In particular, expression of the splice variant of ZAK kinase, ZAK-LF, correlated with PRPF6 levels in colon cancer cells, and further experiments
NATURE REVIEWS | CANCER
NPG
Aberrant splicing promotes colon tumour growth
revealed that PRPF6 is required for alternative splicing of ZAK. Moreover, they showed that the expression of ZAK-LF transformed immortalized mouse fibroblasts and ZAK-LF knockdown reduced the growth of PRPF6‑overexpressing colon cancer cells in vitro and in xenografts. This study identifies PRPF6 as an important driver of colon cancer cell growth and suggests it promotes proliferation by preferential splicing of growth-promoting genes. Isabel Lokody ORIGINAL RESEARCH PAPER Adler, A. S. et al. An integrative analysis of colon cancer identifies an essential function for PRPF6 in tumor growth. Genes Dev. http://dx.doi.org/10.1101/ gad.237206.113 (2014)
VOLUME 14 | JUNE 2014 © 2014 Macmillan Publishers Limited. All rights reserved
