A global analysis of Caenorhabditis elegans operons

Abstract

The nematode worm Caenorhabditis elegans and its relatives are unique among animals in having operons. Operons are regulated multigene transcription units, in which polycistronic pre-messenger RNA (pre-mRNA coding for multiple peptides) is processed to monocistronic mRNAs. This occurs by 3' end formation and trans-splicing using the specialized SL2 small nuclear ribonucleoprotein particle for downstream mRNAs. Previously, the correlation between downstream location in an operon and SL2 trans-splicing has been strong, but anecdotal. Although only 28 operons have been reported, the complete sequence of the C. elegans genome reveals numerous gene clusters. To determine how many of these clusters represent operons, we probed full-genome microarrays for SL2-containing mRNAs. We found significant enrichment for about 1,200 genes, including most of a group of several hundred genes represented by complementary DNAs that contain SL2 sequence. Analysis of their genomic arrangements indicates that >90% are downstream genes, falling in 790 distinct operons. Our evidence indicates that the genome contains at least 1,000 operons, 2 8 genes long, that contain about 15% of all C. elegans genes. Numerous examples of co-transcription of genes encoding functionally related proteins are evident. Inspection of the operon list should reveal previously unknown functional relationships.

Metastatic lymph node 64 (MLN64), a gene overexpressed in breast cancers, is regulated by Sp/KLF transcription factors

“…Recently, growing evidence suggests that genes are not randomly distributed along chromosomes. In fact, the clustering of nonhomologous genes coexpressed under similar conditions and involved in common biological processes has been described in worms (Blumenthal et al, 2002), flies (Boutanaev et al, 2002;Cohen et al, 2000) and mammals (Soury et al, 2001;Lercher et al, 2002). These findings suggest that to achieve a complex biological pathway, the coordinate expression of several clustered genes present in open chromatin regions may be advantageous.…”

Function prediction and protein networks

“…One observation is the presence of polycistronic RNA transcripts in nematodes which were recently estimated to contain 15% of the genes [47 ]. The evidence for functional interactions between the proteins encoded by such polycistronic transcripts is, however, anecdotal.…”

Sequences necessary for trans-splicing in transiently transfected Brugia malayi

“…It involves the addition of a small leader RNA sequence, known as the spliced leader, to the 5′ end of many pre-mRNAs. Trans-splicing appears to serve a variety of different functions, including processing of poly-cistronic pre-mRNAs [2], mRNA cap addition [3,4], polishing and sanitizing the 5′ end of primary transcripts, resulting in optimal spacing for translation [5] and addition of an in-frame start codon [6].…”

“…In the free living nematode Caenorhabditis elegans, the SL1 is added to premRNAs transcribed from singlet genes and genes which are in the 5′ most position in operons. In C. elegans and some other nematodes, the downstream genes of operons are resolved through the addition of a distinct SL sequence, known as the SL2 [2]. However, in other nematodes, including the human filaria, SL2 trans-splicing appears not to exist, and all transcripts, including those located downstream in operon-like structures, contain SL1 [8].…”