Gene silencing, either through a process known as RNA interference
or the methylation of DNA, is now among the hottest topics in
molecular biology and has been called a new regulatory paradigm in
biology. The phenomenon occurs naturally as a gene regulatory
mechanism in plants, and animals, and pathogically as an inhibitor of
tumor suppressor genes in cancer cells. In functional genomics, gene
silencing also shows extraordinary promise as a means of achieving
selective interference of gene function and loss-of-function screens
on a genome-wide scale.
The list of top 20 papers in gene silencing reflects the diverse
nature of this widely occurring phenomenon. One major theme in the
list is the elucidation of the mechanisms of RNA interference:
unraveling the process by which double-stranded RNA is cleaved into
short RNA strands known as siRNA, which in turn work as sequence
specific mediators of gene silencing. Another major theme is the
analysis of how gene silencing is accomplished in the chromatin of
mammalian cells through the methylation of DNA. A quartet of the top
papers examine the role of gene silencing in plants as a gene
regulator and viral protection mechanism, as well as the
counter-mechanisms by which viruses work to suppress
post-transcriptional gene silencing. Other highly cited papers discuss
the role of DNA hypermethylation as a mechanism of tumor-suppressor
inactivation in cancer, and the promise of using gene silencing to
interfere selectively with gene function in a wide range of organisms.
To construct this database,
papers were extracted based on TOPIC search. The keywords used were as follows:
The baseline time span for this database
is 1993-2003 (fourth bimonthly). The resulting database contained 1,505 papers;
4,540 authors; 48 countries; 365 journals; and 898 institutions.
Once the database was in place,
it was used to generate the lists of top 20 papers, authors, journals,
institutions, and nations, covering a time span of 1993-2003 (fourth
The top 20 papers are ranked according to total cites. Rankings for author, journal, institution, and country are listed in three ways: according to total cites, total papers, and total cites/paper. The paper thresholds used to determine scientist, institution, country, and journal rankings according to total cites/paper were as follows: 7, 6, 7, and 8, respectively. These thresholds correspond to the top 1% of authors, 10% of institutions, 50% of countries and 10% of journals by total papers.