by binding to transcription factors which then cause the DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site. For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase. The mature messenger RNA produced from protein-coding genes contains untranslated regions at both ends which contain binding sites for ribosomes, RNA-binding proteins, miRNA, as well as terminator, and start and stop codons. In addition, most eukaryotic open reading frames contain untranslated introns, which are removed and exons, which are connected together in a process known as RNA splicing. Finally, the ends of gene transcripts are defined by cleavage and polyadenylation (CPA) sites, where newly produced pre-mRNA gets cleaved and a string of ~200 adenosine monophosphates is added at the 3' end. The poly(A) tail protects mature mRNA from degradation and has other functions, affecting translation, localization, and transport of the transcript from the nucleus. Splicing, followed by CPA, generate the final mature mRNA, which encodes the protein or RNA product. Although the general mechanisms defining locations of human genes are known, identification of the exact factors regulating these cellular processes is an area of active research. For example, known sequence features in the 3'-UTR can only explain half of all human gene ends. Many noncoding genes in eukaryotes have different transcription termination mechanisms and they do not have pol(A) tails. Many prokaryotic genes are organized into operons, with multiple protein-coding sequences that are transcribed as a unit. The genes in an operon are transcribed as a continuous messenger RNA, referred to as a polycistronic mRNA. The term cistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by a repressor that can occur in an active or inactive state depending on the presence of specific metabolites. When active, the repressor binds to a DNA sequence at the beginning of the operon, called the operator region, and represses transcription of the operon; when the repressor is inactive transcription of the operon can occur (see e.g. Lac operon). The products of operon genes typically have related functions and are involved in the same regulatory network. Functional definitions Defining exactly what section of a DNA sequence comprises a gene is difficult. Regulatory