RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits
Errors during transcription may play an important role in determining cellular phenotypes: the RNA polymerase error rate is >4 orders of magnitude higher than that of DNA polymerase and errors are amplified >1000-fold due to translation. However, current methods to measure RNA polymera...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/09945 |
| _version_ | 1818018928412065792 |
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| author | Lucas B Carey |
| author_facet | Lucas B Carey |
| author_sort | Lucas B Carey |
| collection | DOAJ |
| description | Errors during transcription may play an important role in determining cellular phenotypes: the RNA polymerase error rate is >4 orders of magnitude higher than that of DNA polymerase and errors are amplified >1000-fold due to translation. However, current methods to measure RNA polymerase fidelity are low-throughout, technically challenging, and organism specific. Here I show that changes in RNA polymerase fidelity can be measured using standard RNA sequencing protocols. I find that RNA polymerase is error-prone, and these errors can result in splicing defects. Furthermore, I find that differential expression of RNA polymerase subunits causes changes in RNA polymerase fidelity, and that coding sequences may have evolved to minimize the effect of these errors. These results suggest that errors caused by RNA polymerase may be a major source of stochastic variability at the level of single cells. |
| first_indexed | 2024-04-14T07:45:12Z |
| format | Article |
| id | doaj.art-617a45dfe1764c5d9682830f844ef536 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:45:12Z |
| publishDate | 2015-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-617a45dfe1764c5d9682830f844ef5362022-12-22T02:05:21ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.09945RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunitsLucas B Carey0Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, SpainErrors during transcription may play an important role in determining cellular phenotypes: the RNA polymerase error rate is >4 orders of magnitude higher than that of DNA polymerase and errors are amplified >1000-fold due to translation. However, current methods to measure RNA polymerase fidelity are low-throughout, technically challenging, and organism specific. Here I show that changes in RNA polymerase fidelity can be measured using standard RNA sequencing protocols. I find that RNA polymerase is error-prone, and these errors can result in splicing defects. Furthermore, I find that differential expression of RNA polymerase subunits causes changes in RNA polymerase fidelity, and that coding sequences may have evolved to minimize the effect of these errors. These results suggest that errors caused by RNA polymerase may be a major source of stochastic variability at the level of single cells.https://elifesciences.org/articles/09945RNA-seqRNA polymerasebiological errorssplicing |
| spellingShingle | Lucas B Carey RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits eLife RNA-seq RNA polymerase biological errors splicing |
| title | RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits |
| title_full | RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits |
| title_fullStr | RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits |
| title_full_unstemmed | RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits |
| title_short | RNA polymerase errors cause splicing defects and can be regulated by differential expression of RNA polymerase subunits |
| title_sort | rna polymerase errors cause splicing defects and can be regulated by differential expression of rna polymerase subunits |
| topic | RNA-seq RNA polymerase biological errors splicing |
| url | https://elifesciences.org/articles/09945 |
| work_keys_str_mv | AT lucasbcarey rnapolymeraseerrorscausesplicingdefectsandcanberegulatedbydifferentialexpressionofrnapolymerasesubunits |