Some Hereditary Agents Are Extremely Small

KEY CONCEPT
-Some very small hereditary agents do not encode polypeptide, but consist of RNA or protein with heritable properties.

Viroids (or subviral pathogens) are infectious agents that cause diseases in some plants. They are very small circular molecules of RNA. Unlike viruses—for which the infectious agent consists of a virion, a genome encapsulated in a protein coat—the viroid RNA is itself the infectious agent. The viroid consists solely of the RNA molecule, which is extensively folded by imperfect base pairing, forming a characteristic rod as shown in FIGURE 1. Mutations that interfere with the structure of this rod reduce the infectivity of the viroid.

FIGURE 1. PSTV RNA is a circular molecule that forms an extensive double-stranded structure, interrupted by many interior loops. The severe and mild forms of PSTV have RNAs that differ at three sites.
A viroid RNA consists of a single molecule that is replicated autonomously and accurately in infected cells. Viroids are categorized into several groups. A particular viroid is assigned to a
group according to sequence similarity with other members of the group. For example, four viroids in the potato spindle tuber viroid (PSTV) group have 70%–83% sequence similarity with PSTV.
Different isolates of a particular viroid strain vary from one another in sequence, which can result in phenotypic differences among infected cells. For example, the “mild” and “severe” strains of PSTV differ by three nucleotide substitutions.
Viroids are similar to viruses in that they have heritable nucleic acid genomes, but differ from viruses in both structure and function. Viroid RNA does not appear to be translated into polypeptide, so it cannot itself encode the functions needed for its survival. This situation poses two as yet unanswered questions: How does viroid RNA replicate, and how does it affect the phenotype of the infected plant cell?
Replication must be carried out by enzymes of the host cell. The heritability of the viroid sequence indicates that viroid RNA is the template for replication.
Viroids are presumably pathogenic because they interfere with normal cellular processes. They might do this in a relatively random way—for example, by taking control of an essential enzyme for their own replication or by interfering with the production of necessary cellular RNAs. Alternatively, they might behave as abnormal regulatory molecules, with particular effects upon the expression of individual host cell genes.
An even more unusual agent is the cause of scrapie, a degenerative neurological disease of sheep and goats. The disease is similar to the human diseases of kuru and Creutzfeldt–Jakob disease, which affect brain function. The infectious agent of scrapie does not contain nucleic acid. This extraordinary agent is called a prion (proteinaceous infectious agent). It is a 28 kD hydrophobic glycoprotein, PrP. PrP is encoded by a cellular gene (conserved among the mammals) that is expressed in normal brain cells. The protein exists in two forms: The version found in normal brain cells is called PrP^c and is entirely degraded by proteases; the version found in infected brains is called PrP and is extremely resistant to degradation by proteases. PrP^c is converted to PrP^c  by a conformational change that confers protease-resistance and that has yet to be fully defined.
As the infectious agent of scrapie, PrP^c must in some way modify the synthesis of its normal cellular counterpart so that it becomes infectious instead of harmless . Mice that lack a PrP gene cannot develop scrapie, which demonstrates that PrP is essential for development of the disease.

مواضيع ذات صلة

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Introduction to Noncoding RNA

Prions Cause Diseases in Mammals

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